Pharmacological modification of 12 0 tetradecanoylphorbol 13 acetate induced inflammation and epidermal cell proliferation in mouse skin. (1989 Mar)
pharmacological modification of 12 0 tetradecanoylphorbol 13 acetate induced inflammation and epidermal cell proliferation in mouse skin . topical application of TPA to mouse skin causes oedema ( 2 6 h ) neutrophil influx ( 3 24 h ) and epidermal cell proliferation ( 24 48 h ) . topical application of a cyclooxygenase inhibitor ( indomethacin ) dual cyclooxygenase and lipoxygenase inhibitors ( phenidone and bw755c ) a selective lipoxygenase inhibitor ( aa861 ) , protein synthesis inhibitors ( cycloheximide and actinomycin D ) or a glucocorticosteroid ( prednisolone ) inhibited oedema and neutrophil influx . systemic administration of an inhibitor of microtubule assembly ( colchicine ) also prevented neutrophil influx and oedema . these results suggest that the inflammatory response to TPA depends on an interaction between a protein and products of arachidonic acid metabolism to produce a neutrophil dependent oedema . epidermal cell proliferation was inhibited by topical administration of prednisolone , indomethacin , bw755c and cycloheximide but not systemically administered methotrexate . This suggests that inhibition of the early inflammatory response to TPA prevents the subsequent epidermal proliferation .

Heme induces neutrophil migration and reactive oxygen species generation through signaling pathways characteristic of chemotactic receptors. (2007 Aug)
Heme induces neutrophil migration and reactive oxygen species generation through signaling pathways characteristic of chemotactic receptors . hemolysis or extensive cell damage can lead to high concentrations of free heme , causing oxidative stress and inflammation . considering that heme induces neutrophil chemotaxis , we hypothesize that heme activates a G protein coupled receptor . Here we show that similar to heme , several heme analogs were able to induce neutrophil migration in vitro and in vivo . mesoporphyrins , molecules lacking the vinyl groups in their rings , were not chemotactic for neutrophils and selectively inhibited heme induced migration . moreover , migration of neutrophils induced by heme was abolished by pretreatment with pertussis toxin , an inhibitor of galpha inhibitory protein , and with inhibitors of phosphoinositide 3 kinase , phospholipase cbeta , mitogen activated protein kinases , or Rho kinase . The induction of reactive oxygen species by heme was dependent of galpha inhibitory protein and phosphoinositide 3 kinase and partially dependent of phospholipase cbeta , protein kinase C , mitogen activated protein kinases , and Rho kinase . together , our results indicate that heme activates neutrophils through signaling pathways that are characteristic of chemoattractant molecules and suggest that mesoporphyrins might prove valuable in the treatment of the inflammatory consequences of hemorrhagic and hemolytic disorders .

Endothelial adhesion molecules and their role in inflammation. (1993 Jul)
endothelial adhesion molecules and their role in inflammation . The emigration of leukocytes such as neutrophils into inflammatory sites requires adhesion to the endothelium of small venules . The initial adhesive event is margination characterized by rolling of neutrophils along the luminal surface of the endothelium . Each member of the selectin family of adhesion molecules has been shown to support neutrophil rolling under conditions of flow . E selectin is synthesized by endothelial cells following cytokine stimulation , P selectin is rapidly mobilized from weibel palade bodies to the endothelial cell surface following stimulation with agents such as histamine , and L selectin is constitutively expressed on the surface of leukocytes . Each selectin functions primarily as a lectin , recognizing carbohydrate structures on the leukocyte or endothelial cell surface . Once the marginated neutrophil forms a stationary adhesion with endothelial cells , it is stimulated by chemotactic factors to downregulate the selectin based adhesion and upregulate adherence dependent on beta 2 integrins , principally cd11a / CD18 ( LFA 1 ) and cd11b / CD18 ( Mac 1 ) . these adhesion molecules interact with intercellular adhesion molecule 1 ( ICAM 1 ) and possibly other structures on the endothelial cell , and the leukocyte rapidly emigrates into surrounding tissue . transendothelial migration in vitro is markedly inhibited by monoclonal antibodies against CD18 integrins or ICAM 1 . monoclonal antibodies against the selectins , CD18 , cd11a , cd11b , and ICAM 1 have all been shown to …

Accumulation of the neutrophil derived protein YKL 40 during storage of various blood components. (2001 Apr)
accumulation of the neutrophil derived protein YKL 40 during storage of various blood components . objective AND design : Post transfusion infectious complications associated with allogeneic blood components may depend on storage time and may be related to extracellular accumulation of bioactive substances during storage . YKL 40 is a glycoprotein located in the specific granules of the neutrophils . while exocytosed it may play a role in inflammation and remodelling of the extracellular matrix . We studied the potential accumulation of YKL 40 in blood components during storage . methods : using a RIA method extracellular accumulation of YKL 40 was determined in supernatants from whole blood , plasma reduced whole blood , buffy coat depleted SAGM ( saline adenine glucose mannitol ) blood , whole blood leukocyte depleted by prestorage filtration , and whole blood leukocyte depleted by bedside filtration . The blood was donated by volunteer , healthy blood donors , and stored under standard blood bank conditions for 35 days . results : extracellular accumulation of YKL 40 increased significantly in a time dependent manner during storage for 35 days of non filtered whole blood , plasma reduced whole blood , and SAGM blood , respectively . prestorage leukocyte depletion of whole blood prevented extracellular YKL 40 accumulation , while YKL 40 accumulation was not reduced by bedside leukocyte depletion . conclusion : YKL 40 appears to accumulate extracellularly in a time dependent manner in standard erythrocyte components . prestorage leukocyte depletion by filtration of whole …

Lung transplant ischemia reperfusion injury : metalloprotease inhibition down regulates exposure of type V collagen , growth related oncogene induced … (2008 Mar)
Lung transplant ischemia reperfusion injury : metalloprotease inhibition down regulates exposure of type V collagen , growth related oncogene induced neutrophil chemotaxis , and tumor necrosis factor alpha expression . background : immunity to type V collagen col ( V ) contributes to lung transplant rejection . matrix metalloproteases ( MMPs ) , which are induced by transplant related ischemia reperfusion injury ( IRI ) , could expose col ( V ) and regulate local IRI induced inflammation . methods : To test the hypothesis that MMPs induce col ( V ) exposure and inflammation , wistar kyoto rats were treated with the MMP inhibitor , COL 3 , before inducing lung IRI without transplantation , and in parallel studies , wistar kyoto lung donor and recipients were treated with COL 3 pre and postisograft lung transplantation . results : ischemia reperfusion injury induced growth related oncogene / CINC 1 dependent neutrophil influx , and up regulated tumor necrosis factor alpha . MMP2 and MMP9 , induced at 4 and 24 hr after IRI , respectively , were associated with detection of antigenic col ( V ) in bronchoalveolar lavage and lung interstitium because of MMP mediated matrix degradation . MMP inhibitor treatment significantly reduced polymorphonuclear leukocytes , growth related oncogene / CINC 1 , and tumor necrosis factor alpha ; abrogated MMP 9 expression ; and resulted in lower levels of antigenic col ( V ) in bronchoalveolar lavage . In the lung transplant model , inhibiting MMPs in …

Inhibition of tumour necrosis factor alpha ( TNF alpha ) induced neutrophil respiratory burst by a TNF inhibitor. (1991 Jun)
inhibition of tumour necrosis factor alpha ( TNF alpha ) induced neutrophil respiratory burst by a TNF inhibitor . tumour necrosis factor alpha ( TNF alpha ) plays an important role in microbial defence and tissue damage by activating neutrophils . therefore the ability of natural molecules to regulate the activity of TNF alpha is likely to be of major importance in our understanding of the mechanisms of inflammation . We have examined the effects of a highly purified urine derived TNF inhibitor ( TNF inh ) on the TNF alpha induced respiratory burst in human neutrophils . TNF alpha inh treated TNF alpha was unable to stimulate a neutrophil lucigenin dependent chemiluminescence response and superoxide formation . treatment of TNF with the inhibitor also significantly reduced the priming ability of TNF alpha for a response to the peptide f met leu phe . these results show that the ability of TNF alpha to induce a key neutrophil response is amenable to regulation by the TNF alpha inh .

Interferon gamma induction of pulmonary emphysema in the adult murine lung. (2000 Dec)
interferon gamma induction of pulmonary emphysema in the adult murine lung . chronic inflammation containing CD8 ( ) lymphocytes , neutrophils , and macrophages , and pulmonary emphysema coexist in lungs from patients with chronic obstructive pulmonary disease . although this inflammatory response is believed to cause the remodeling that is seen in these tissues , the mechanism ( s ) by which inflammation causes emphysema have not been defined . Here we demonstrate that interferon gamma ( IFN gamma ) , a prominent product of CD8 ( ) cells , causes emphysema with alveolar enlargement , enhanced lung volumes , enhanced pulmonary compliance , and macrophage and neutrophil rich inflammation when inducibly targeted , in a transgenic fashion , to the adult murine lung . prominent protease and antiprotease alterations were also noted in these mice . They included the induction and activation of matrix metalloproteinase ( MMP ) 12 and cathepsins B , H , D , S , and L , the elaboration of MMP 9 , and the selective inhibition of secretory leukocyte proteinase inhibitor . IFN gamma causes emphysema and alterations in pulmonary protease / antiprotease balance when expressed in pulmonary tissues .

Expression of cell adhesion molecules in the lungs of patients with idiopathic pulmonary fibrosis. (1995 Aug)
expression of cell adhesion molecules in the lungs of patients with idiopathic pulmonary fibrosis . idiopathic pulmonary fibrosis ( IPF ) is a chronic inflammatory disorder restricted to the lungs . leukocyte entry into the area of inflammation is regulated , at least partly , by endothelial expression of leukocyte selective cell adhesion molecules ( CAMs ) . To investigate the relevance of these CAMs to the accumulation of leukocytes in IPF , we examined the expression of E selectin ( endothelial leukocyte adhesion molecule 1 ; ELAM 1 ) , intercellular adhesion molecule 1 ( ICAM 1 ) , and vascular cell adhesion molecule 1 ( VCAM 1 ) by immunohistochemistry in lung tissue from nine patients with IPF and five nonsmoking normal subjects . The results demonstrated that in normal lungs , ICAM 1 was weakly expressed on endothelial cells , but neither E selectin nor VCAM 1 was detected . In the lungs of patients with IPF , E selectin expression on endothelial cells was restricted to honeycombing regions . endothelial expression of ICAM 1 was increased throughout the tissue , but VCAM 1 was not detected in IPF . The distribution of leukocytes in lungs with IPF consisted of mostly lymphocyte accumulation in the interstitium and neutrophil accumulation within the airspaces of honeycomb regions . these results suggest that E selectin may play a role in the recruitment of neutrophils in regions of honeycombing and that ICAM 1 may play a role in lymphocyte recruitment into …

Isolation of two polypeptides comprising the neutrophil immobilizing factor of human leucocytes. (1983 Feb)
isolation of two polypeptides comprising the neutrophil immobilizing factor of human leucocytes . human leucocyte lysosomal polypeptides of mol . wt 4000 5000 , which constitute the neutrophil immobolizing factor ( NIF ) , were isolated from the 22 , 000 g supernate of sonicates of human neutrophils by filtration on sephadex G 75 . The larger ( NIF 1 ) and smaller ( NIF 2 ) of the polypeptides were resolved by filtration on Bio Gel P6 and purified to homogeneity by sequential reverse phase high performance liquid chromatography and paper electrophoresis . The results of analyses of amino acid composition indicated that NIF 1 and NIF 2 are distinct polypeptides composed of an apparent total of 41 and 38 amino acids , respectively . Both NIF polypeptides contain one cysteine and one methionine , lack isoleucine , tyrosine and phenylalanine , and are rich in histidine and proline . The sequence of 20 of the amino terminal amino acids of both NIF polypeptides is identical , but NIF 2 possesses an additional alanine at the amino terminus . highly purified NIF 1 and NIF 2 inhibited human neutrophil random migration and chemotaxis to diverse stimuli in a concentration dependent manner , with 50 inhibition of chemotaxis by 0 . 31 1 x 10 ( 8 ) M NIF 1 and 1 3 x 10 ( 7 ) M NIF 2 . neither NIF polypeptide was cytotoxic for neutrophils , altered neutrophil phagocytosis or release of lysosomal enzymes , …

Lucigenin induced chemiluminescence in human neutrophils in the process of chemotactic migration measured in a modified boyden chamber. (1989 Oct)
lucigenin induced chemiluminescence in human neutrophils in the process of chemotactic migration measured in a modified boyden chamber . To the question of whether an oxidative metabolism of neutrophils occurs in the process of chemotactic migration , we have already demonstrated that formyl peptide and zymosan activated serum effectively induced lucigenin dependent chemiluminescence ( CL ) in a specially devised boyden chamber . In the present study we confirmed this and , furthermore , demonstrated that superoxide dismutase partially suppressed the neutrophil chemotaxis to formyl peptide and concanavalin A , suggesting the participation of superoxide in a chemotactically migrating mechanism . however , monocyte derived chemotactic factor did not cause any light emission , irrespective of its chemotactic activity . based on these results , neutrophil chemotactic factors seem to be divided into two types , that is , oxidative metabolism related and nonrelated . To the former group of chemotactic factors a premature activation of oxidative metabolism in neutrophils may start even at the initial stage of chemotaxis , and these primed cells may respond with a respiratory burst to higher concentrations of the chemoattractant itself or to other chemical mediators present at the site of inflammation .

Monocyte activation in patients with wegener s granulomatosis. (1999 Jun)
monocyte activation in patients with wegener s granulomatosis . objective : wegener s granulomatosis ( WG ) is an inflammatory disorder characterised by granulomatous inflammation , vasculitis , and necrotising vasculitis and is strongly associated with anti neutrophil cytoplasmic antibodies ( ANCA ) . activated monocytes / macrophages are present in renal biopsy specimens and participate in granuloma formation by synthesising and secreting a variety of chemoattractants , growth factors , and cytokines . In view of these findings , in vivo monocyte activation was evaluated in patients with WG and the findings related to parameters of clinical disease activity . methods : monocyte activation was analysed by measuring plasma concentrations of soluble products of monocyte activation , that is neopterin and interleukin 6 ( IL6 ) , by elisa , and by quantitating the surface expression of activation markers on circulating monocytes by flow cytometry . results : twenty four patients with active WG were included in this study . Ten of these patients were also analysed at the time of remission . twelve patients with sepsis served as positive controls , and 10 healthy volunteers as negative controls for monocyte activation . patients with active disease had increased monocyte activation compared with healthy controls as shown by increased concentrations of neopterin ( p 0 . 0001 ) and increased surface expression of cd11b ( p 0 . 05 ) and CD64 ( p 0 . 05 ) . In those patients with increased concentrations of IL6 during active …

Increased serum concentration of urinary trypsin inhibitor with asthma exacerbation. (2003 Nov)
increased serum concentration of urinary trypsin inhibitor with asthma exacerbation . The aim of the study was to determine whether the amount of urinary trypsin inhibitor ( UTI ) in serum , a degenerate induced by neutrophil elastase ( NE ) , reflects the degree of bronchial inflammation in children with acute asthma exacerbation . The involvement of neutrophil mediated inflammation plays as important a role as eosinophil mediated inflammation in the pathogenesis of acute asthma exacerbation . however , no measurable marker is sensitive enough to assess neutrophil mediated inflammation in the airways . The pre alpha / inter alpha trypsin inhibitors are assumed to be precursors of UTI . NE degrades pre alpha / inter alpha trypsin inhibitors to liberate UTI . UTI concentrations in 25 childhood patients admitted with asthma exacerbation and 15 control subjects were measured by means of one step sandwich type enzyme immunoassay . serum UTI concentrations in the patients at admission were significantly higher than control values ( 10 . 597 / 0 . 649 and 6 . 136 / 0 . 303 U x mL ( 1 ) , respectively ( mean / SEM ) ) . these levels returned to baseline values with improvement in the asthmatic symptoms . however , serum NE and alpha1 antitrypsin concentrations were not significantly different between patients and controls , even during acute exacerbation in the former . The findings suggest that neutrophil mediated inflammatory events are involved in exacerbation of childhood asthma . The …

Neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose related fashion. (2001 Apr)
neutrophil defensins mediate acute inflammatory response and lung dysfunction in dose related fashion . High concentrations of neutrophil defensins from airway and blood have been reported in patients with inflammatory lung diseases , but their exact role is unclear . We investigated the direct effect of defensins on the lungs of mice . intratracheal instillation of purified defensins ( 5 30 mg / kg ) induced a progressive reduction in peripheral arterial O ( 2 ) saturation , increased lung permeability , and enhanced the lung cytochrome c content . these indexes of acute lung dysfunction were associated with an increased total cell number and a significant neutrophil influx into the lung 5 . 1 / 0 . 04 in control vs . 48 . 6 / 12 . 7 in the defensin ( 30 mg / kg ) group , P 0 . 05 . elastase concentrations in the bronchoalveolar lavage ( BAL ) fluids increased from 38 / 11 ng / ml ( control ) to 80 / 4 ng / ml ( defensins , P 0 . 05 ) . Five hours after defensin instillation , concentrations of tumor necrosis factor alpha and macrophage inflammatory protein 2 in BAL fluid were significantly increased . High levels of monocyte chemoattractant protein 1 in BAL fluid and plasma were also found after defensin stimulation . We conclude that intratracheal instillation of defensins causes acute lung inflammation and dysfunction , suggesting that high concentrations of defensins in the airways may …

Cytokine regulated expression of activated leukocyte cell adhesion molecule ( cd166 ) on monocyte lineage cells and in rheumatoid arthritis … (1999 Feb)
cytokine regulated expression of activated leukocyte cell adhesion molecule ( cd166 ) on monocyte lineage cells and in rheumatoid arthritis synovium . objective : To determine whether monocyte / macrophage expression of the CD6 ligand , activated leukocyte cell adhesion molecule ( alcam ) ( cd166 ) , is regulated by cytokines during inflammation in rheumatoid arthritis ( RA ) . methods : We used flow cytometry to test whether cytokines present in rheumatoid synovium could regulate alcam cell surface expression on peripheral blood ( PB ) monocytes and RA synovial fluid ( SF ) macrophages , and we examined alcam expression in situ in RA synovium by immunofluorescence . results : The monocyte differentiation factors interleukin 3 , macrophage colony stimulating factor ( M CSF ) , and granulocyte macrophage colony stimulating factor augmented alcam expression on PB monocytes . alcam was expressed on monocyte lineage cells in situ in inflamed synovium from patients with RA ( 9 of 9 ) , but not in uninflamed synovium from patients with joint trauma ( 0 of 3 ) . furthermore , in vitro culture induced alcam expression on PB monocytes and CD14 RA SF cells was inhibited by an M CSF neutralizing antibody . conclusion : alcam expression on PB and SF monocytes / macrophages is enhanced by M CSF .

Expression of elastase and fibrin in venous leg ulcer biopsies : a pilot study of pentoxifylline versus placebo. (1996 Sep)
expression of elastase and fibrin in venous leg ulcer biopsies : a pilot study of pentoxifylline versus placebo . The pathogenesis of venous leg ulcers is based on the leakage of fibrinogen leading to a pericapillary fibrin cuff and plugging of capillaries by white blood cells . On the basis of a previous work , we had assumed that the key event in the pathogenesis of venous leg ulcers is related to inflammation generated by activated white blood cells that accumulate under unrelieved blood pressure , because in ulcer biopsies we had detected the presence of tumor necrosis factor alpha ( TNF alpha ) in intracapillary monocytes , elastase in the polymorphonuclear leukocytes near the vessels , and a pericapillary undegraded fibrin cuff causing a diffusion barrier to oxygen . This concept was developed because TNF alpha synthesized by activated monocytes is responsible for many deleterious effects . It has a potent mitogenic effect on fibroblasts , leading to new collagen deposition and angiogenesis , it induces an increase in collagenase production , it acts through upregulation of an intracellular adhesion molecule ( ICAM 1 ) , leading to leukocyte sequestration and consequently a release of toxic metabolites by the polymorphonuclear cells , an early step in chronic inflammation , it activates the coagulation pathway via a marked increase in monocyte associated tissue factor ( TF ) procoagulant activity , and it inhibits fibrinolysis by promoting the release of PAI 1 , contributing to undegraded fibrin deposition . therefore , …

Pentoxifylline and lung ischemia reperfusion injury : application to lung transplantation. (1996 Sep)
pentoxifylline and lung ischemia reperfusion injury : application to lung transplantation . université paris Sud Lung transplant group . pentoxifylline ( PTX ) attenuates neutrophil mediated lung injury in several models of acute lung inflammation . because pulmonary neutrophil sequestration is the main determinant of ischemia reperfusion ( IR ) injury in lung transplantation , we sought to determine whether or not PTX prevented IR injury in isolated perfused rat and rabbit lungs submitted to IR , and in pigs after left lung allotransplantation . In rat lungs after IR , the coefficient of lung endothelial permeability ( Kfc ) increased by 112 / 12 in controls and by 27 / 8 ( p 0 . 001 ) in PTX treated lungs . after IR , lung myeloperoxidase and blood neutrophil count decrease were lower with PTX than in controls , and the changes in Kfc were correlated with the percentage decrease in blood neutrophils during reperfusion . In rabbit lungs , endothelium dependent relaxation in isolated pulmonary arterial rings was decreased in the control group and normal in the PTX group . In pigs ventilated with pure oxygen , the PaO2 was greater in the PTX group than in the control group ( 423 / 49 vs . 265 / 43 mm Hg ; p 0 . 05 ) , whereas the total pulmonary vascular resistance was lower ( 15 / 1 vs . 30 / 9 mm Hg / L / min ; p 0 . 02 ) …

Leukocyte activation study during occlusive arterial disease of the lower limb : effect of pentoxifylline infusion. (1996 Sep)
leukocyte activation study during occlusive arterial disease of the lower limb : effect of pentoxifylline infusion . granulocytes play a significant role in vascular diseases . The mechanisms of neutrophil mediated vascular injury include their increased endothelial adhesion and activation with release of inflammatory mediators . pentoxifylline ( PTX ) has a well demonstrated ability to act on the activated neutrophils . It increases chemotaxis and decreases their adherence to endothelial cells , oxidative burst , and enzyme release . In this preliminary study , we investigated the effects of PTX on ischemia induced changes in polymorphonuclear neutrophils ( PMN ) activation and cytokine release . A double blind , randomized , placebo controlled trial was carried out in 14 patients ( age range 46 86 years ) suffering from critical ischemia , as defined by the european consensus document , or subacute ischemia due to occlusive arterial disease of the lower limb . femoral and antecubital venous blood samples on the side of the ischemic leg were obtained from patients immediately before ( TO ) and after infusion ( T24 ) of PTX or placebo . PMN activation was evaluated by study of cell migration , beta 2 integrin expression ( cd11b / CD18 ) , oxidative burst , and elastase release . inflammation proteins were analyzed , such as tumor necrosis factor alpha ( TNF alpha ) , interleukin 1 ( IL 1 ) , interleukin 6 ( IL 6 ) , C reactive protein ( CRP ) …

Effect of IL 1 blockade on inflammatory manifestations of acute ventilator induced lung injury in a rabbit model. (1995 Jul)
effect of IL 1 blockade on inflammatory manifestations of acute ventilator induced lung injury in a rabbit model . ventilator induced lung injury in children and adults is characterized by an initial inflammatory phase . To investigate whether the inflammatory cytokine , IL 1 , plays a role in this process , a rabbit model of ventilator induced injury was created . animals maintained under pentobarbital anesthesia were primed for injury by undergoing lung lavage with 22 mL / kg of saline and then ventilated for 8 h with either FIO2 0 . 21 and normal pressures or FIO2 1 . 0 and high ventilator pressures . The animals exposed to hyperoxia / hyperventilation demonstrated a greater increase in lung lavage neutrophil counts and a higher histological injury score , as well as a faster decline in oxygenation compared to the control animals . A third group of rabbits received 800 micrograms of recombinant IL 1 receptor antagonist after lung lavage and prior to the exposure to FIO2 1 . 0 and high ventilator pressures . these animals had significantly lower concentrations of albumin and elastase and lower neutrophil counts in their lungs after the 8 h ventilatory period compared to hyperoxia / hyperventilation rabbits . IL 1 blockade had no effect on the decline in dynamic compliance and oxygenation seen in saline treated hyperoxic / hyperventilated rabbits . IL 1 is a mediator of acute inflammation due to ventilator induced lung injury .

Selective regulation of metalloproteinase inhibitor ( TIMP 1 ) by oncostatin M in fibroblasts in culture. (1993 Jul)
selective regulation of metalloproteinase inhibitor ( TIMP 1 ) by oncostatin M in fibroblasts in culture . tissue inhibitor of metalloproteinases ( TIMP 1 ) is a potent inhibitor of activated matrix metalloproteinases ( MMP ) such as collagenase , stromelysin , and gelatinase , and thus helps to control extracellular matrix metabolism and deposition by connective tissue cells . since various cytokines and growth factors can modify the production of MMP and TIMP 1 , we explored the action of oncostatin M ( OM ) , a unique lymphocyte and monocyte derived cytokine , on expression of these proteins . We examined the regulation of TIMP 1 expression in cultured human fibroblasts by cytokines including OM , IL 6 , leukemia inhibitory factor ( LIF ) , and IL 1 alpha . When used at levels of 5 to 50 ng / ml , OM , IL 6 , LIF , and IL 1 alpha elevated the TIMP 1 expression at the RNA level in fibroblasts of lung or synovial origin . interestingly , OM stimulation resulted in highest levels of TIMP 1 RNA and protein synthesis . however , unlike IL 1 alpha , the cytokines OM , IL 6 , and LIF did not induce MMP or PGE2 release . OM also enhanced TIMP 1 mRNA levels in the h2981 lung carcinoma and hepg2 hepatoma cell lines . The results suggest that OM as well as IL 6 and LIF , other cytokines acting through similar receptor …

Pulmonary epithelial cells facilitate TNF alpha induced neutrophil chemotaxis. (1994 May)
pulmonary epithelial cells facilitate TNF alpha induced neutrophil chemotaxis . A role for cytokine networking . TNF alpha and neutrophils are postulated to play important roles in several inflammatory lung diseases . Thus , we examined TNF alpha induced neutrophil migration through polycarbonate filters and human pulmonary type II like epithelial ( A549 ) cells cultured as monolayers on these filters . TNF alpha induced both dose and time dependent migration of neutrophils across both barriers , but migration across A549 cells was much greater than that across naked filters . migration of neutrophils across both barriers was completely inhibited by anti TNF alpha . furthermore , supernatants of TNF alpha ( 10 ( 9 ) M ) stimulated A549 monolayers induced threefold greater migration of neutrophils across naked filters than 10 ( 9 ) M TNF alpha itself , suggesting release of soluble chemotactic factor ( s ) . pretreatment of A549 monolayers with actinomycin D inhibited both the production of soluble chemotactic factors and TNF alpha induced transcellular migration . supernatants from TNF alpha stimulated A549 cells contained significant concentrations of IL 8 , and coincubation of these supernatants with anti IL 8 decreased supernatant induced chemotaxis . finally , coincubation of TNF alpha with anti IL 8 during transmigration experiments partially inhibited neutrophil migration through A549 monolayers . therefore , pulmonary type II epithelial cells facilitate TNF alpha induced transcellular migration of neutrophils through the production of soluble protein synthesis dependent chemotactic factors , including IL 8 …