Association of the polymorphism of macrophage migration inhibitory factor gene with coronary heart disease in chinese population objective : inflammation … (2006 Oct)
association of the polymorphism of macrophage migration inhibitory factor gene with coronary heart disease in chinese population objective : inflammation is involved in the process of coronary heart disease ( CHD ) . macrophage migration inhibitory factor ( MIF ) is a proinflammatory cytokine which can inhibit the random migration of macrophages and concentrate macrophages at the inflammatory site , and is thought to play an important role in cell mediated immunity . The present study is to investigate the association of the 173 G / C polymorphism of MIF gene with the outcome of the CHD . methods : One hundred and thirty eight patients with coronary angiography ( CAG ) proved CHD were studied , and 163 healthy matched controls in guangdong were studied . patients and controls were genotyped for a single nucleotide polymorphism in the 5 flanking region at position 173 of the MIF gene , using PCR RFLP analysis , followed by DNA sequencing identification . results : Only MIF 173G / G and MIF 173G / C genotypes were detected in CHD patients and controls . The MIF 173 G allele was detected in 0 . 966 of normal controls and 0 . 917 of patients , while MIF 173 C allele was detected in 0 . 034 of normal controls and 0 . 083 of patients . individuals possessing a MIF 173 C genotype have an increased risk of CHD ( 16 . 7 versus 6 . 8 ) ( OR : 2 …

Macrophage migration inhibitory factor ( MIF ) contributes to the development of allergic rhinitis. (2005 Jul)
macrophage migration inhibitory factor ( MIF ) contributes to the development of allergic rhinitis . macrophage migration inhibitory factor ( MIF ) is a proinflammatory cytokine whose expression has been found to be critical to the generation of antigen specific immune responses . recent studies suggested that MIF played a role in the initiation and maintenance of allergic diseases . To elucidate MIF s role in the pathogenesis of allergic rhinitis ( AR ) , we sensitized MIF deficient gene knockout ( KO ) mice and wild type ( WT ) mice intraperitoneally with ovalbumin ( OVA ) and compared their clinical symptoms and allergic responses after intranasal challenge . antigen induced nasal symptoms were significantly reduced in MIF KO mice compared to WT mice . histological examination of nasal mucosa showed that the number of infiltrating eosinophils in MIF KO mice was significantly lower than that in WT mice ( P 0 . 05 ) . The concentration of TNF alpha in nasal mucosa was also significantly lower in MIF KO mice than in WT mice ( P 0 . 05 ) . We have demonstrated that the absence of MIF affects several aspects of experimental AR . One mechanism by which these effects might be mediated is by down regulating TNF alpha . The block of allergic inflammation in MIF KO mice suggests that MIF may play a role in the allergic response .

Human thioredoxin 1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production. (2006 Oct)
human thioredoxin 1 ameliorates experimental murine colitis in association with suppressed macrophage inhibitory factor production . background AIMS : thioredoxin 1 ( TRX ) is a small multifunctional protein with antioxidative and redox regulating functions . In this study , we investigated the significance of TRX in patients with inflammatory bowel disease ( IBD ) and the ability and mechanism to ameliorate experimental colitis . methods : serum TRX and macrophage migration inhibitory factor ( MIF ) levels were measured in patients with IBD . The effects of TRX were evaluated in a dextran sulfate sodium ( DSS ) induced colitis model by comparing TRX overexpressing transgenic ( TRX TG ) and control mice . We further evaluated the effect of recombinant human TRX ( rhtrx ) administration on DSS induced colitis and colonic inflammation of interleukin ( IL ) 10 knockout ( IL 10 KO ) mice . colonic inflammation was examined clinically and histologically . proinflammatory cytokine levels were examined in colonic tissues , and MIF levels were measured in colonic tissues and sera in mice . The effect of TRX on MIF production was also analyzed in vitro . results : serum TRX and MIF levels were significantly higher in patients with IBD than normal controls , and TRX levels correlated with disease activity . TRX significantly ameliorated DSS induced colitis and colonic inflammation of IL 10 KO mice . increase of tumor necrosis factor alpha and interferon gamma in colonic tissues was significantly suppressed in TRX …

Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat. (2007 Mar)
Sex steroid regulation of macrophage migration inhibitory factor in normal and inflamed colon in the female rat . background AND AIMS : Sex steroids influence IBD symptoms . macrophage migration inhibitory factor ( MIF ) , a target of sex steroids in other inflammatory models , promotes interleukin ( IL ) 1beta and tumor necrosis factor ( TNF ) alpha release in colitis . We investigated whether estradiol and progesterone influence MIF , IL 1beta , and TNF alpha production in experimental colitis . methods : colonic MIF , IL 1beta , and TNF alpha levels were measured in cyclic and ovariectomized rats , with or without estradiol benzoate ( EB ) or progesterone ( P ) replacement . MIF distribution was assessed by immunohistochemistry . cytokines , myeloperoxidase activity , macroscopic damage , and plasma corticosterone were assessed 24 hours after intrarectal trinitrobenzene sulfonic acid ( TNBS ) , with and without neutralizing anti MIF antibody . effects of EB and P on myeloperoxidase activity and MIF concentration were also assessed at 7 days in dextran sulfate sodium induced colitis . results : basal IL 1beta and TNF alpha contents did not fluctuate during the estrous cycle , while MIF concentrations increased from estrus ( estrogen dominance ) to metestrus ( P dominance ; P . 05 ) . EB and P treatment mimicked these effects in ovariectomized rats , and similarly altered MIF immunostaining . progesterone dominance aggravated TNBS colitis in comparison with estrogen . progesterone enhanced TNBS …

Suppressive effect of bradykinin to cellular immune responses in vivo and in vitro. (1983 Jul)
suppressive effect of bradykinin to cellular immune responses in vivo and in vitro . bradykinin , as well as histamine , one of the mediators in IgE mediated immediate type allergic reactions or acute inflammation , may affect the in vitro and in vivo cell mediated immune reactions of the immunized animals . It was demonstrated in our present experiment that the appearance of delayed type hypersensitivity ( DTH ) skin reaction in the immunized guinea pig was remarkably suppressed by treatment of bradykinin or histamine and the suppression of cutaneous DTH by bradykinin was inhibited by H 2 antagonist ( burimamide ) but not by H 1 receptor blocker ( chlorpheniramine ) . It was also clearly demonstrated that bradykinin suppressed the production of antigen induced macrophage migration inhibitory factor ( MIF ) of the immune guinea pig peritoneal exudate cells ( PECs ) and the production of MIF was blocked by H 2 antagonist ( burimamide ) or H 2 agonist ( tolazolin ) but not by H 1 antagonist ( chlorpheniramine ) . antigen induced lymphocyte proliferation of the immunized mice , one of the indicators of the cellular immune response , was also suppressed by treatment of bradykinin . these results indicate that bradykinin as well as histamine may have some role in the subsequent expression of cellular immune reactions .

A proinflammatory cytokine inhibits p53 tumor suppressor activity. (1999 Dec)
A proinflammatory cytokine inhibits p53 tumor suppressor activity . p53 has a key role in the negative regulation of cell proliferation , in the maintenance of genomic stability , and in the suppression of transformation and tumorigenesis . To identify novel regulators of p53 , we undertook two functional screens to isolate genes which bypassed either p53 mediated growth arrest or apoptosis . In both screens , we isolated cdnas encoding macrophage migration inhibitory factor ( MIF ) , a cytokine that was shown previously to exert both local and systemic proinflammatory activities . treatment with MIF overcame p53 activity in three different biological assays , and suppressed its activity as a transcriptional activator . The observation that a proinflammatory cytokine , MIF , is capable of functionally inactivating a tumor suppressor , p53 , may provide a link between inflammation and tumorigenesis .

Is macrophage migration inhibitory factor a therapeutic target in systemic lupus erythematosus ? systemic lupus erythematosus ( SLE ) is … (2003 Sep)
Is macrophage migration inhibitory factor a therapeutic target in systemic lupus erythematosus ? systemic lupus erythematosus ( SLE ) is the prototype of a cluster of diseases that are characterized by a loss of self tolerance and chronic inflammation in organs including skin , kidney , brain and joints . researchers have long debated the varying contributions of the components of the immune system to the pathogenesis of SLE , but the emigration of leucocytes from the microcirculation , and the subsequent tissue inflammation mediated by these inflammatory cells , are key features of chronic inflammation seen in SLE . macrophage migration inhibitory factor ( MIF ) is a broad spectrum pro inflammatory cytokine . We hypothesize that MIF is an important inflammatory mediator in the perpetuation of immune activation in SLE , via its effects on activation of T and B cells , and endothelial and effector cells . As MIF exerts anti apoptotic effects , it may also play a role in promoting abnormal survival of autoreactive lymphocytes , thus perpetuating autoimmune reactivity . In addition , MIF has a unique relationship with glucocorticoids , in that MIF can override the effects of glucocorticoids and may be important in steroid resistance . By virtue of its pluripotent functions , we propose that MIF may be a critical mediator of inflammation and damage in SLE , and that targeting of MIF may offer therapeutic benefits in this disease .

Japanese encephalitis virus up regulates expression of macrophage migration inhibitory factor ( MIF ) mRNA in the mouse brain. (2001 Jan)
japanese encephalitis virus up regulates expression of macrophage migration inhibitory factor ( MIF ) mRNA in the mouse brain . macrophage migration inhibitory factor ( MIF ) is known as a proinflammatory cytokine , glucocorticoid induced immunomodulator , and pituitary hormone , and contributes to broad spectrum immune and inflammatory response . To investigate the expression of MIF in the central nervous system in an event of viral infection , we evaluated MIF mRNA expression in the mouse brain infected with japanese encephalitis virus ( JEV ) . In situ hybridization revealed that MIF mRNA expression was significantly up regulated in the whole brain by intracranial JEV inoculation at 2 days post inoculation ( d . p . i . ) . neurons as well as glial cells expressed MIF transcripts in which some of these cells were co labeled by double staining for JEV antigens and MIF mRNA . At 4 d . p . i . , when typical symptoms of encephalitis were observed , JEV antigen positive cells were much increased in parallel with enhanced MIF mRNA , consistent with the results of northern blot analysis . reverse transcription polymerase chain reaction showed that MIF mRNA was minimally changed at 1 d . p . i . in comparison with that at 0 d . p . i . , but markedly up regulated after 2 d . p . i . and sustained up to 4 d . p . i . On the other hand …

ISO 1 binding to the tautomerase active site of MIF inhibits its pro inflammatory activity and increases survival in severe … (2005 Oct)
ISO 1 binding to the tautomerase active site of MIF inhibits its pro inflammatory activity and increases survival in severe sepsis . MIF is a proinflammatory cytokine that has been implicated in the pathogenesis of sepsis , arthritis , and other inflammatory diseases . antibodies against MIF are effective in experimental models of inflammation , and there is interest in strategies to inhibit its deleterious cytokine activities . Here we identify a mechanism of inhibiting MIF pro inflammatory activities by targeting MIF tautomerase activity . We designed small molecules to inhibit this tautomerase activity ; a lead molecule , ISO 1 ( ( S , R ) 3 ( 4 hydroxyphenyl ) 4 , 5 dihydro 5 isoxazole acetic acid methyl ester ) , significantly inhibits the cytokine activity in vitro . moreover , ISO 1 inhibits tumor necrosis factor release from macrophages isolated from lpstreated wild type mice but has no effect on cytokine release from mifdeficient macrophages . The therapeutic importance of the MIF inhibition by ISO 1 is demonstrated by the significant protection from sepsis , induced by cecal ligation and puncture in a clinically relevant time frame . these results identify ISO 1 as the first small molecule inhibitor of MIF proinflammatory activities with therapeutic implications and indicate the potential of the MIF active site as a novel target for therapeutic interventions in human sepsis .

Enhancement of monocyte transendothelial migration by granulocyte macrophage colony stimulating factor : requirement for chemoattractant and cd11a / CD18 mechanisms. (1999 Dec)
enhancement of monocyte transendothelial migration by granulocyte macrophage colony stimulating factor : requirement for chemoattractant and cd11a / CD18 mechanisms . granulocyte macrophage colony stimulating factor ( GM CSF ) enhances and primes monocyte functions , but its role in monocyte migration is poorly understood . We examined monocyte migration across human umbilical vein endothelial cells ( huvec ) grown on filters . GM CSF had no chemotactic or chemokinetic effect . however , GM CSF enhanced monocyte transendothelial migration ( TEM ) through unstimulated and IL 1 activated ( 5 h ) huvec in response to C5a or monocyte chemoattractant protein 1 in a dose dependent fashion , increasing the migration from 28 . 7 / 5 . 3 to 41 . 8 / 6 . 2 ( n 8 , p 0 . 05 ) and from 34 . 8 / 6 to 50 . 3 / 3 . 1 , p 0 . 05 ) , respectively . The enhanced TEM was inhibited by monoclonal antibodies ( mAb ) to LFA 1 , but not by mAb to Mac 1 or to VLA 4 . furthermore , GM CSF up regulated and activated LFA 1 , as assessed by NKI L16 neoepitope expression . The results indicate that : ( 1 ) GM CSF can prime monocytes for increased TEM , ( 2 ) GM CSF enhances LFA 1 mediated monocyte TEM and ( 3 ) this effect is in part mediated by increasing LFA 1 expression …

Spironolactone prevents diabetic nephropathy through an anti inflammatory mechanism in type 2 diabetic rats. (2006 Apr)
spironolactone prevents diabetic nephropathy through an anti inflammatory mechanism in type 2 diabetic rats . aldosterone induces myocardial fibrosis and vascular inflammation via proinflammatory and profibrotic cytokines . The effect of spironolactone on renal inflammation and renal function was investigated in type 2 diabetic rats . For define the molecular mechanism of spironolactone , the effect of spironolactone on the synthesis of monocyte chemotactic peptide 1 ( MCP 1 ) and its upstream transcription factor , NF kappab , was evaluated in cultured mesangial cells and proximal tubular cells . there were no changes in blood glucose concentration or BP after spironolactone treatment . spironolactone treatment significantly reduced urinary albumin excretion and ameliorated glomerulosclerosis . urinary levels of MCP 1 were significantly increased concurrently with renal expression of MCP 1 , macrophage migration inhibitory factor , and macrophage infiltration . spironolactone treatment significantly inhibited urinary excretion of MCP 1 as well as renal MCP 1 and migration inhibitory factor expression and macrophage infiltration . In addition , aldosterone induced upregulation of MCP 1 expression and NF kappab transcriptional activity in cultured cells , and spironolactone reduced both NF kappab activation and MCP 1 synthesis . furthermore , NF kappab inhibition abolished aldosterone induced MCP 1 production . overall , these findings suggest that aldosterone induced NF kappab activation leads to activation of proinflammatory cytokines , ultimately leading to renal injury in this model . these data suggest that mineralocorticoid blockade may be a potential therapeutic target in diabetic nephropathy .

The effect of helicobacter pylori infection on expression of macrophage migration inhibitory factor by T cells and macrophages in gastric … (2005 Aug)
The effect of helicobacter pylori infection on expression of macrophage migration inhibitory factor by T cells and macrophages in gastric mucosa . background : macrophage migration inhibitory factor ( MIF ) plays a pivotal role in inflammatory and immune mediated diseases . however , its molecular function and role in gastrointestinal diseases has rarely been studied and thus warrants an in depth investigation . This study was designed and conducted to determine MIF expression in helicobacter pylori ( H . pylori ) induced gastritis and the effect of H . pylori on MIF expression in monocytes in vitro . methods : gastric specimens of 62 patients with chronic gastritis were obtained through endoscopic biopsies . Both gastric antrum and body were examined for histopathologic changes . positive H . pylori was determined through rapid urease test and histopathological examination . A patient was classified as H . pylori positive if both tests showed positive results . The updated sydney system was employed to assess the severity and activity of gastric inflammation . double immunoassaying for MIF / T cells ( cd45ro ) and MIF / macrophage ( KP1 ) , as well as in situ hybridization for the expression of MIF mRNA were used for the current analysis . THP 1 , a monocyte cell line , was co incubated with H . pylori strains ( atcc26695 ) and subsequently examined for the expression of MIF protein and mRNA by enzyme linked immunosorbent assay and retrospective transcription polymerase chain reaction …

Functional polymorphisms in the promoter region of macrophage migration inhibitory factor and chronic gastritis. (2007 Sep)
functional polymorphisms in the promoter region of macrophage migration inhibitory factor and chronic gastritis . macrophage migration inhibitory factor ( MIF ) is a key proinflammatory mediator , which plays a pivotal role in inflammatory and immune diseases . We attempted to clarify associations of the functional polymorphisms of the MIF gene promoter with the development of chronic gastritis . The study was performed with 290 stocked DNAs from subjects with no evidence of gastric malignancy . We employed the PCR SSCP method to detect gene polymorphisms . The severity of histological chronic gastritis in antral biopsy specimens was classified according to the updated sydney system . Both the 7 / 7 CATT repeat at position 794 and the 173 C / C genotypes were significantly associated with a risk of developing severe gastric mucosal atrophy ( OR , 9 . 69 ; 95 CI , 1 . 29 72 . 5 ; and OR , 4 . 60 ; 95 CI , 1 . 05 20 . 2 , respectively ) . In subjects younger than 60 years old , the number of 7 CATT alleles was significantly correlated with both the activity and inflammation scores ( p 0 . 0079 and 0 . 0080 , respectively ) . Our results suggested that functional promoter polymorphisms of the MIF gene might be associated with the severity of gastric mucosal inflammation in younger subjects and with the subsequent development of mucosal atrophy .

Macrophage migration inhibitory factor governs endothelial cell sensitivity to LPS induced apoptosis. (2008 Jun)
macrophage migration inhibitory factor governs endothelial cell sensitivity to LPS induced apoptosis . human endothelial cells ( EC ) are typically resistant to the apoptotic effects of stimuli associated with lung disease . The determinants of this resistance remain incompletely understood . macrophage migration inhibitory factor ( MIF ) is a proinflammatory cytokine produced by human pulmonary artery EC ( hpaec ) . Its expression increases in response to various death inducing stimuli , including lipopolysaccharide ( LPS ) . We show here that silencing MIF expression by RNA interference ( MIF sirna ) dramatically reduces MIF mRNA expression and the LPS induced increase in MIF protein levels , thereby sensitizing hpaecs to LPS induced cell death . addition of recombinant human MIF ( rhmif ) protein prevents the death sensitizing effect of MIF sirna . A common mediator of apoptosis resistance in ECs is the death effector domain ( DED ) containing protein , FLIP ( flice like inhibitory protein ) . We show that LPS induces a transcription independent increase in the short isoform of FLIP ( FLIP ( s ) ) . This increase is blocked by MIF sirna but restored with the addition of recombinant MIF protein ( rhmif ) . while FLIP ( s ) sirna also sensitizes hpaecs to LPS induced death , the addition of rhmif does not affect this sensitization , placing MIF upstream of FLIP ( s ) in preventing hpaec death . these studies demonstrate that MIF is an endogenous …

Macrophage migration inhibitory factor : controller of systemic inflammation. (2006 Aug)
macrophage migration inhibitory factor : controller of systemic inflammation . macrophage migration inhibitory factor ( MIF ) is a cytokine that is secreted by the anterior pituitary and immune cells in response to surgical stress , injury , and sepsis . This cytokine appears to be a critical regulator of the inflammatory pathways , leading to systemic inflammatory response syndrome and subsequent multiple organ dysfunction syndrome . This report provides an integrated scheme describing the manner by which MIF controls the neurohormonal response and the adaptive immune system , namely the T helper ( Th ) 1 and Th2 lymphocytes , which results in the release of pro inflammatory cytokines and the anti inflammatory cytokine interleukin 10 . The development of systemic inflammatory response syndrome and subsequent development of multiple organ dysfunction syndrome appear to be related to MIF levels and the balance of Th1 and Th2 function .

The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle. (2000 Dec)
The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle . severe infection or tissue invasion can provoke a catabolic response , leading to severe metabolic derangement , cachexia , and even death . macrophage migration inhibitory factor ( MIF ) is an important regulator of the host response to infection . released by various immune cells and by the anterior pituitary gland , MIF plays a critical role in the systemic inflammatory response by counterregulating the inhibitory effect of glucocorticoids on immune cell activation and proinflammatory cytokine production . We describe herein an unexpected role for MIF in the regulation of glycolysis . The addition of MIF to differentiated L6 rat myotubes increased synthesis of fructose 2 , 6 bisphosphate ( F2 , 6BP ) , a positive allosteric regulator of glycolysis . increased expression of the enzyme 6 phosphofructo 2 kinase / fructose 2 , 6 bisphosphatase ( PFK 2 ) enhanced F2 , 6BP production and , consequently , cellular lactate production . The catabolic effect of TNF alpha on myotubes was mediated by MIF , which served as an autocrine stimulus for F2 , 6BP production . TNF alpha administered to mice decreased serum glucose levels and increased muscle F2 , 6BP levels ; pretreatment with a neutralizing anti MIF mAb completely inhibited these effects . Anti MIF also prevented hypoglycemia and increased muscle F2 , 6BP levels in TNF alpha knockout mice that were administered LPS , supporting the intrinsic contribution of MIF …

Interferon gamma induces macrophage migration inhibitory factor synthesis and secretion by tubular epithelial cells. (2004 Mar)
interferon gamma induces macrophage migration inhibitory factor synthesis and secretion by tubular epithelial cells . macrophage migration inhibitory factor ( MIF ) promotes macrophage accumulation and leucocyte activation during inflammation . macrophage migration inhibitory factor is upregulated in intrinsic renal cells in many types of kidney diseases , and has a pathogenic role in rat crescentic nephritis . however , little is known about the factors that regulate the production and secretion of MIF in kidney cells . In this study , we evaluated whether interferon gamma ( IFN gamma ) , a cytokine implicated in the development of kidney disease and a potent inducer of MIF production in macrophages , could promote MIF synthesis and secretion from renal tubular epithelial cells . northern blot analysis detected constitutive expression of MIF mRNA in rat tubular epithelial cells ( nrk52e ) , which increased twofold after a 6 h stimulation with IFN gamma . macrophage migration inhibitory factor protein was found only in the cytoplasm of nrk52e cells . following IFN gamma stimulation , intracellular MIF in nrk52e cells was rapidly secreted with a maximal reduction of 50 after 20 min , which returned to normal levels after 2 4 h . rapid secretion of MIF in response to IFN gamma was also seen in rat mesangial cells . these findings indicate that IFN gamma induces rapid secretion of MIF by tubular epithelial cells , and suggest that this may be an important mechanism leading to inflammatory cell accumulation and activation …

Macrophage migration inhibitory factor and the discovery of tautomerase inhibitors. (2002 Jun)
macrophage migration inhibitory factor and the discovery of tautomerase inhibitors . macrophage migration inhibitory factor ( MIF ) is a pro inflammatory cytokine released from T cells and macrophages , and is a key molecule in inflammation . although a detailed understanding of the biological functions of MIF has not yet been found , it is known that MIF catalyzes the tautomerization of phenylpyruvate and a non physiological molecule , D dopachrome . A potent tautomerase inhibitor would be expected , as a validation tool , to shed light on role of MIF activity and the relationship between its biological and enzymatic activity . Such tautomerase inhibitors would be useful in the treatment of MIF related diseases , such as sepsis , acute respiratory distress syndrome ( ARDS ) , asthma , atopic dermatitis , rheumatoid arthritis ( RA ) , nephropathy and tumors . In this review , we have focused on ( 1 ) the biological and enzymatic activities of MIF , ( 2 ) the discovery of novel , drug like tautomerase inhibitors of MIF using a structure based computer assisted search , and ( 3 ) a crystallographic and molecular modeling study of the MIF tautomerase inhibitor complexes ( A review with 133 references ) .

Reduction of the aortic inflammatory response in spontaneous atherosclerosis by blockade of macrophage migration inhibitory factor ( MIF ). (2005 Dec)
reduction of the aortic inflammatory response in spontaneous atherosclerosis by blockade of macrophage migration inhibitory factor ( MIF ) . atherosclerosis is an inflammatory response of the arterial wall to injury , which is prominently driven by cytokines . The inflammatory mediator macrophage migration inhibitory factor ( MIF ) is a unique cytokine that was recently associated with atherogenesis . Here , we have investigated whether MIF has a role in spontaneous atherosclerosis by studying apolipoprotein E deficient ( ApoE ( / ) ) mice treated with neutralizing anti MIF monoclonal antibody and comparison with isotype IgG treated controls . after 14 weeks , the aortas and heart valves were analyzed for inflammatory status , macrophage content and plaque areas . MIF expression in the aortic wall was elevated upon spontaneous atherogenesis , with foam cells representing a major source . Of note , MIF blockade led to a marked reduction in intimal Mac 1 positive macrophages . similarly , treatment with anti MIF antibody led to a reduction of a variety of inflammatory mediators typically associated with atherosclerosis including the circulating levels of fibrinogen , MIF and IL 6 . importantly , the local aortic expression of ICAM 1 , MMP 2 , TNF , IL 12 , and cd40l was reduced by MIF blockade , as were the levels of the phospho c Jun and C / ebpbeta transcription factors . The observed strong reduction of inflammatory parameters by anti MIF treatment was associated with a small , …

Substance P induced release of macrophage migration inhibitory factor from rat bladder epithelium. (2004 Mar)
substance P induced release of macrophage migration inhibitory factor from rat bladder epithelium . purpose : substance P ( SP ) , a neuropeptide mediator of neurogenic inflammation , induces vasodilatation , plasma extravasation and hypersensitivity in the bladder . SP induced inflammation is enhanced and maintained by the release of additional mediators . The rat urothelium contains pre formed macrophage migration inhibitory factor ( MIF ) , a known proinflammatory cytokine , suggesting that it may mediate bladder neurogenic inflammation . We documented the time course of SP effects on rat bladder inflammation . materials AND methods : subcutaneous SP administration induced neurogenic inflammation . The bladder , urine and serum were removed 15 , 30 , 60 and 120 minutes following treatment , and changes in MIF , nerve growth factor ( NGF ) , c fos and cox 2 were determined . results : SP induced significant MIF and NGF release from the bladder following 30 minutes of exposure . cox 2 protein was detected at significant levels following 60 minutes of SP exposure . basal c fos protein could be detected in control bladders with significant increases following 60 minutes of SP exposure . histological examination of bladder tissue showed increased edema in SP treated bladders . conclusions : SP stimulated early release of urothelial MIF as well as increased MIF gene expression in this model of neurogenic inflammation . SP also increased expression of the proinflammatory mediator NGF . In addition , increases in cox …