Interaction of inflammation mediators ( myeloperoxidase and defensin ) with mixed monolayers from lens lipids and crystallins accumulation of inflammation … (1992 Apr)
interaction of inflammation mediators ( myeloperoxidase and defensin ) with mixed monolayers from lens lipids and crystallins accumulation of inflammation mediators ( myeloperoxidase and defensin ) on lens membranes was studied in a model system . For this purpose ability of these proteins to interact with mixed monolayers from the lens lipids and lens proteins ( crystallins ) was appreciated .

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 .

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 …

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 …

Regional location of alpha 1 antichymotrypsin and alpha 1 antitrypsin genes on human chromosome 14. (1986 May)
regional location of alpha 1 antichymotrypsin and alpha 1 antitrypsin genes on human chromosome 14 . The human protease inhibitor genes alpha 1 antitrypsin ( alpha 1 PI ) and alpha 1 antichymotrypsin ( alpha 1 ACT ) are acute phase proteins which are induced in response to inflammation . these inhibitors function to limit the activity of serine proteases in vivo . alpha 1 PI acts as an inhibitor of neutrophil elastase to protect the elastin fibers of the lung . genetic deficiencies of alpha 1 PI result in development of chronic pulmonary emphysema . The physiologic role of alpha 1 ACT has not been clearly defined , but it also appears to function in the maintenance of protease protease inhibitor equilibrium in the lung . nucleic acid and protein sequence homologies detected between alpha 1 PI and alpha 1 ACT suggested an evolutionary relationship . Gene mapping experiments were performed to determine if these protease inhibitor genes reside at the same chromosomal locus in man . In situ hybridization data demonstrate that both alpha 1 PI and alpha 1 ACT map to the same region , q31 q32 . 3 , on chromosome 14 .

Neutrophil chemotactic factor in supernatant from pulmonary fibroblasts stimulated with cytokines fibroblasts are important for maintenance of the structural frame … (1993 Jul)
neutrophil chemotactic factor in supernatant from pulmonary fibroblasts stimulated with cytokines fibroblasts are important for maintenance of the structural frame network for most tissues , and they also play an important role in the inflammatory process via production of various mediators . In this study , we demonstrated that pulmonary fibroblasts may participate in pulmonary inflammation by production of neutrophil chemotactic factor ( NCF ) . pulmonary fibroblasts were stimulated with various cytokines ( IGF 1 , PDGF , IL 1 alpha , IL 1 beta , IL 2 , IL 6 , TNF , IFNr ) . fibroblasts stimulated with either TNF , IL 1 alpha or IL beta but not IGF , PDGF , IL 2 or IL 6 demonstrated a kinetic and dose dependent increase in NCF activity . The NCF activity of crude supernatant was heat stable and was not changed by anti C5 antibody treatment or ether extraction . characterization of the NCF activity by gel filtration using high pressure liquid chromatography showed two active fractions , one with MW greater than 100 kD and the other with MW less than 10 kD . NCF activity in the small molecular weight fraction was demonstrated by inhibition of chemotaxis by addition of anti IL 8 antibody . these data suggest that cytokine treated fibroblast derived NCF may be important in the pathogenesis and expression of a variety of pulmonary disease processes associated with neutrophil accumulation and activation .

The role of rat cytokine induced neutrophil chemoattractants ( cincs ) in inflammation Rat cytokine induced neutrophil chemoattractants ( cincs … (2002 Apr)
The role of rat cytokine induced neutrophil chemoattractants ( cincs ) in inflammation Rat cytokine induced neutrophil chemoattractants ( cincs ) are the members of the CXC chemokine family . Four neutrophil chemokines , CINC 1 , CINC 2 alpha , CINC 2 beta and CINC 3 , were purified from the conditioned medium of granulation tissue culture . CINC 2 alpha and CINC 2 beta differ only in the sequence of three carboxy terminal residues and are produced by alternative splicing . CINC 3 had neutrophil chemotactic activity similar to that of CINC 1 and CINC 2 , but induced greater calcium mobilization than CINC 1 and CINC 2 . CINC 1 , 2 and 3 induced calcium flux in cxcr2 transfected hek293 cells . In addition , anti cxcr2 serum inhibited neutrophil chemotactic activities of the three types of cincs almost completely . these results indicate that rat cxcr2 is a unique receptor for CINC 1 , 2 and 3 . cincs induced calcium mobilization through pertussis toxin insensitive G protein but induced chemotaxis through pertussis toxin sensitive G protein . CINC 1 / 2 and CINC 3 may stimulate both G proteins with distinct efficiency . The concentration of CINC 1 increased transiently in rat air pouch / lipopolysaccharide inflammation , whereas the CINC 2 level increased linearly . The number of infiltrated cells increased up to 8 h . The increase in cell number was correlated with the total concentration of CINC 1 and CINC 2 …

Effect of exogenous opioid peptides on TNF alpha induced human neutrophil apoptosis in vitro. (2003 Sep)
effect of exogenous opioid peptides on TNF alpha induced human neutrophil apoptosis in vitro . polymorphonuclear leukocyte ( neutrophil ) apoptosis is an important mechanism regulating the life span and some functions of neutrophils at inflamed sites . opioid peptides are present in the peripheral circulation and their concentrations rapidly increase as a result of stress and inflammation . The effect of opioid peptides such as met enkephalin ( M ENK ) and beta endorphin ( beta END ) on tumor necrosis factor ( TNF ) alpha induced apoptosis in human neutrophils in vitro was investigated . neutrophils isolated from peripheral blood were cultured in the absence or presence of 10 ( 6 ) 10 ( 10 ) M of opioid peptides for 8 , 12 and 18 h . features of apoptotic neutrophils were measured by a flow cytometric method based on analysis of the apoptotic nuclei ( DNA content ) . We found that M ENK and beta END enhanced both uninduced and TNF alpha induced neutrophil apoptosis in vitro in a dose dependent manner . The effect of opioid peptides on the modulation of neutrophil apoptosis was not reversed by the opioid receptor antagonist naloxone . The results suggest that M ENK and beta END can regulate neutrophil life span via apoptosis and in this way may participate in the resolution of inflammation .

Rat gastric mucosal cells express ICAM 1 and proinflammatory cytokines during indomethacin induced mucosal injury. (1998 Jul)
Rat gastric mucosal cells express ICAM 1 and proinflammatory cytokines during indomethacin induced mucosal injury . adhesion molecules and cytokines are known to be involved in the formation of acute gastric mucosal injury . however , it is not clear whether the gastric mucosal cells express these molecules and modulate the inflammation . To clarify whether gastric mucosal cells express intercellular adhesion molecule 1 ( ICAM 1 ) and proinflammatory cytokines ( tumor necrosis factor alpha ( TNF alpha ) , interleukin 1 alpha ( IL 1 alpha ) , and cytokine induced neutrophil chemoattractant 2 beta ( CINC 2 beta ) ) in the formation of gastric mucosal injury , we have used rat indomethacin induced gastric mucosal lesions as an in vivo model . The gene expression of all cytokines and ICAM 1 increases at the early stages of indomethacin induced gastritis ( TNF alpha and IL 1 alpha gene expression began to increase earlier than that of ICAM 1 and CINC 2 beta ) and can mainly be detected in the gastric epithelial layer . To further identify the source of those molecules , the epithelial cells were separated into seven fractions according to their sizes by a counterflow elution . ICAM 1 and CINC 2 beta gene expressions are particularly enhanced in the middle sized cell fractions that are rich in gastric mucous producing cells . The effect of TNF alpha or IL 1 alpha on the gene expression of ICAM 1 and cytokines was examined …

Regulation of lipopolysaccharide induced lung inflammation by plasminogen activator inhibitor 1 through a JNK mediated pathway. (2005 Sep)
regulation of lipopolysaccharide induced lung inflammation by plasminogen activator inhibitor 1 through a JNK mediated pathway . The neutrophil is of undoubted importance in lung inflammation after exposure to LPS . We have shown recently that systemic inhibition of JNK decreased neutrophil recruitment to the lung after exposure to LPS , although the mechanisms underlying this inhibition are incompletely understood . As plasminogen activator inhibitor 1 ( PAI 1 ) accentuates cell migration , with JNK activation recently shown to up regulate PAI 1 expression , this suggested that systemic JNK inhibition may down regulate LPS induced pulmonary neutrophil recruitment through a decrease in PAI 1 expression . We show in this study that exposure of mice to aerosolized LPS increased PAI 1 expression in the lung and alveolar compartment , which was decreased by pretreatment with the JNK inhibitor sp600125 . exogenous , intratracheally administered PAI 1 prevented the inhibition of pulmonary neutrophil recruitment in the setting of systemic JNK inhibition , thereby suggesting a role for PAI 1 in the JNK mediated pathway regulating LPS induced neutrophil recruitment . In addition , PAI 1 ( / ) mice had a decrease in neutrophil recruitment to the alveolar compartment after exposure to LPS , compared with wild type controls , further suggesting a role for PAI 1 in LPS induced lung inflammation . An increase in the intravascular level of KC is a likely mechanism for the inhibition of pulmonary neutrophil recruitment after LPS exposure in the setting of …

Beta defensin overexpression induces progressive muscle degeneration in mice. (2007 Jun)
Beta defensin overexpression induces progressive muscle degeneration in mice . defensins comprise a family of cationic antimicrobial peptides characterized by conserved cysteine residues . They are produced in various organs including skeletal muscle and are identified as key elements in the host defense system as potent effectors . At the same time , defensins have potential roles in the regulation of inflammation and , furthermore , can exert cytotoxic effects on several mammalian cells . Here , we developed transgenic mice overexpressing mouse beta defensin 6 to explore the pathophysiological roles of the defensin family as a novel mediator of inflammatory tissue injury . unexpectedly , the transgenic mice showed short lifespan , poor growth , and progressive myofiber degeneration with functional muscle impairment , predominant centronucleated myofibers , and elevated serum creatine kinase activity , as seen in human muscular dystrophy . furthermore , some of the transgenic myofibers showed ikappabalpha accumulation , which would be related to the myofiber apoptosis of limb girdle muscular dystrophy type 2A . The present findings may unravel a concealed linkage between the innate immune system and the pathophysiology of degenerative diseases .

The link module from human TSG 6 inhibits neutrophil migration in a hyaluronan and inter alpha inhibitor independent manner. (2002 Dec)
The link module from human TSG 6 inhibits neutrophil migration in a hyaluronan and inter alpha inhibitor independent manner . TSG 6 protein ( the secreted product of the tumor necrosis factor stimulated gene 6 ) , a hyaluronan binding protein comprised mainly of a Link and CUB module arranged in a contiguous fashion , has been shown previously to be a potent inhibitor of neutrophil migration in an in vivo model of acute inflammation ( wisniewski , H . G . , Hua , J . C . , poppers , D . M . , naime , D . , vilcek , J . , and cronstein , B . N . ( 1996 ) J . immunol . 156 , 1609 1615 ) . It was hypothesized that this activity of TSG 6 was likely to be mediated by its potentiation of inter alpha inhibitor anti plasmin activity ( causing a down regulation of the protease network ) , which was reliant on these proteins forming a stable , probably covalent approximately 120 kDa complex . Here we have shown that the recombinant Link module from human TSG 6 ( Link TSG6 ; expressed in escherichia coli ) has an inhibitory effect on neutrophil influx into zymosan A stimulated murine air pouches , equivalent to that of full length protein ( which we produced in a drosophila expression system ) . The active dose of 1 microg of Link TSG6 per mouse ( administered intravenously ) also …

Aerosol alpha 1 antitrypsin treatment for cystic fibrosis. (1991 Mar)
aerosol alpha 1 antitrypsin treatment for cystic fibrosis . In cystic fibrosis neutrophil dominated inflammation on the respiratory epithelial surface results in a chronic epithelial burden of the destructive enzyme , neutrophil elastase . alpha 1 antitrypsin ( alpha 1AT ) , the main inhibitor of neutrophil elastase in lung , was given in aerosol form to 12 cystic fibrosis patients . It suppressed neutrophil elastase in the respiratory epithelial lining fluid ( ELF ) and restored the ELF anti neutrophil elastase capacity when ELF alpha 1AT reached 8 mumol / l . This treatment also reversed the inhibitory effect of cystic fibrosis ELF on pseudomonas killing by neutrophils , which suggests that it may augment host defence in cystic fibrosis .

Modulation of cell adhesion molecule expression and function on human lung microvascular endothelial cells by inhibition of phosphodiesterases 3 and … (1998 Aug)
modulation of cell adhesion molecule expression and function on human lung microvascular endothelial cells by inhibition of phosphodiesterases 3 and 4 . 1 . expression of cell adhesion molecules ( CAM ) on the lung microvascular endothelium is believed to play a key role in the recruitment of leukocytes in pulmonary inflammation . moreover , regulation of CAM expression may be an important mechanism through which this inflammation may be controlled . experimental evidence has suggested that combined phosphodiesterase ( PDE ) 3 and 4 inhibitors increase cyclic AMP levels within cells greater than inhibition of either isoenzyme alone . In the present study we assessed the effect of combinations of rolipram ( PDE4 inhibitor ) , ORG 9935 ( PDE3 inhibitor ) and salbutamol ( beta agonist ) on CAM expression and neutrophil or eosinophil adhesion to human lung microvascular endothelial cells ( hlmvec ) . 2 . tumour necrosis factor alpha ( TNF alpha ) induced intercellular adhesion molecule ( ICAM ) 1 , vascular cell adhesion molecule ( VCAM ) 1 and E selectin expression were measured on hlmvec monolayers at 6 h by a specific elisa technique in the presence of different combinations of medium , rolipram , ORG 9935 and salbutamol . 3 . rolipram in combination with salbutamol , but neither agent alone , inhibited TNF alpha induced E selectin expression , whilst ICAM 1 and VCAM 1 expression were not affected . ORG 9935 had no significant effect on CAM expression alone . …

IL 15 mediates antigen induced neutrophil migration by triggering IL 18 production. (2007 Dec)
IL 15 mediates antigen induced neutrophil migration by triggering IL 18 production . We have investigated the mechanisms underlying IL 15 induced neutrophil migration into inflamed tissues . IL 15 induced neutrophil migration to the peritoneal cavity in mice in a time and dose dependent manner . The cell migration was not induced in IL 18 / , MIP 1alpha ( CCL3 ) / , tnfr1 / or 5 LOX / mice but was normal in IFN gamma / mice . IL 15 induced neutrophil migration was inhibited by anti MIP 2 ( cxcl2 ) antibody or mk886 ( leukotriene synthesis inhibitor ) . IL 18 induced neutrophil migration was also dependent on tnfr1 , MIP 1alpha , MIP 2 and leukotriene . consistent with this observation , IL 15 induced IL 18 production , and IL 15 or IL 18 injection induced the production of MIP 2 , MIP 1alpha , TNF alpha and LTB4 . In an antigen specific inflammation model , ovalbumin ( OVA ) induced neutrophil migration was completely inhibited by soluble IL 15ralpha ( sIL 15ralpha ) or anti MIP 2 antibody . furthermore , cell migration was absent in IL 18 / , MIP 1alpha / , tnfr1 / , or 5 LOX / mice . OVA challenge induced the release of MIP 2 , MIP 1alpha , TNF alpha and LTB4 in the peritoneal cavity in an IL 15 and IL 18 dependent manner . We also found that neutrophils from the peripheral …

Helicobacter pylori negative duodenal ulcer. (1991 Aug)
helicobacter pylori negative duodenal ulcer . purpose patients AND methods : helicobacter pylori ( HP ) is present in more than 90 of duodenal ulcers ( DUs ) . To investigate the pathophysiology in those patients with DU who are HP negative compared with those who are HP positive , we interviewed consecutive patients prior to endoscopy regarding factors often associated with ulcer disease . At esophagogastroduodenoscopy , antral biopsy specimens were obtained for urease test , culture , and warthin starry staining for HP in all patients with DU who did not have active bleeding . results : compared with HP positive patients who had DU , HP negative patients with DU were more likely to be aspirin users and less likely to have had prior ulcers . HP positive patients with DU had more severe antral inflammation than HP negative patients . whites were more likely to be HP negative than blacks . HP negative patients with DU most commonly presented with bleeding , whereas HP positive patients with DU presented with pain . conclusions : Our findings suggest a different mechanism for DUs in patients who are HP positive versus those who are HP negative , and this difference might have a bearing on treatment . The absence of HP should lead to a more thorough search for nonsteroidal anti inflammatory drug / aspirin use , zollinger ellison syndrome , and other potential causes of DUs .

Inhibition of c Jun N terminal kinase limits lipopolysaccharide induced pulmonary neutrophil influx. (2005 Apr)
inhibition of c Jun N terminal kinase limits lipopolysaccharide induced pulmonary neutrophil influx . The influx of neutrophils into the lung is a sentinel event in LPS induced acute lung inflammation . previous studies have shown that systemic inhibition of p38 decreases LPS induced neutrophil influx into the alveolar space but has no effect on pulmonary parenchymal neutrophil accumulation or on microvascular leak , indicating other pathways are important in LPS induced acute lung inflammation . This study examined the role of c Jun N terminal kinase in LPS induced acute lung inflammation . systemic inhibition of c Jun N terminal kinase , with the specific c Jun N terminal kinase inhibitor sp600125 , decreased the LPS induced accumulation of neutrophils into the lung parenchyma and alveolar space . In addition , increases in microvascular leak after LPS exposure were diminished by c Jun N terminal kinase inhibition . To determine mechanisms by which systemic c Jun N terminal kinase inhibition decreased pulmonary neutrophil influx , LPS and tumor necrosis factor alpha ( TNF alpha ) induced neutrophil actin assembly and retention were examined . neutrophil actin assembly was decreased after LPS and TNF alpha stimulation with sp600125 pretreatment , as well as LPS induced neutrophil retention . finally , c Jun N terminal kinase inhibition decreased cdc42 activation after LPS or TNF alpha stimulation , thereby providing one mechanism by which c Jun N terminal kinase inhibition decreased actin assembly , and thereby pulmonary neutrophil accumulation .

Neutrophil defensins stimulate the release of cytokines by airway epithelial cells : modulation by dexamethasone. (2002 Feb)
neutrophil defensins stimulate the release of cytokines by airway epithelial cells : modulation by dexamethasone . objective AND design : neutrophils may contribute to recruiting other cells to sites of inflammation by generating chemotactic signals themselves , or by stimulating other cell types to release chemoattractants such as interleukin 8 ( IL 8 ) . recently , we demonstrated that neutrophil derived alpha defensins are able to increase IL 8 expression in airway epithelial cells . In addition , it has previously been reported that neutrophil elastase induced IL 8 synthesis was insensitive to inhibition by the glucocorticoid dexamethasone . The aim of the present study was to investigate the effect of defensins on the expression of various cytokines in cultured airway epithelial cells and to examine the effect of dexamethasone on defensin induced cytokine synthesis in these cells . methods : cultures of A549 cells and primary bronchial epithelial cells ( PBEC ) were stimulated with defensins either alone or in the presence of dexamethasone . supernatants were analyzed for IL 8 , ENA 78 , IL 6 , MCP 1 and GM CSF by elisa . In addition , IL 8 and ENA 78 mRNA was detected by northern blot analysis . results : defensins increased IL 8 expression , ENA 78 , MCP 1 and GM CSF release from A549 cells , whereas in PBEC only IL 8 and IL 6 were increased . Pre treatment with dexamethasone significantly reduced defensin induced IL 6 , IL 8 …

Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins. (2000 Mar)
regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins . secretory leukocyte proteinase inhibitor ( SLPI ) is a serine proteinase inhibitor that is produced locally in the lung by cells of the submucosal bronchial glands and by nonciliated epithelial cells . Its main function appears to be the inhibition of neutrophil elastase ( NE ) . recently , NE was found to enhance SLPI mRNA levels while decreasing SLPI protein release in airway epithelial cells . furthermore , glucocorticoids were shown to increase both constitutive and NE induced SLPI mRNA levels . In addition to NE , stimulated neutrophils also release alpha defensins . defensins are small , antimicrobial polypeptides that are found in high concentrations in purulent secretions of patients with chronic airway inflammation . Like NE , defensins induce interleukin 8 production in airway epithelial cells . This induction is sensitive to inhibition by the glucocorticoid dexamethasone and is prevented in the presence of alpha ( 1 ) proteinase inhibitor . The aim of the present study was to investigate the effect of defensins on the production of SLPI and the related NE inhibitor elafin / skalp in primary bronchial epithelial cells ( pbecs ) . defensins significantly increase SLPI protein release by pbecs in a time and dose dependent fashion without affecting SLPI mRNA synthesis . In the presence of alpha ( 1 ) proteinase inhibitor , the defensin induced SLPI protein release is further enhanced , but no effect was observed …