Opposing roles for IL 13 and IL 13 receptor alpha 2 in health and disease. (2004 Nov)
opposing roles for IL 13 and IL 13 receptor alpha 2 in health and disease . interleukin ( IL ) 13 is a key inducer of several type 2 cytokine dependent pathologies . It regulates inflammation , mucus production , tissue remodeling , and fibrosis . consequently , it has become an important therapeutic target for a number of debilitating illnesses , including asthma , idiopathic pulmonary fibrosis , ulcerative colitis , as well as several other diseases in which IL 13 is believed to be overproduced . In the murine model of schistosomiasis , IL 13 has emerged as a central mediator of chronic infection induced liver pathology . although IL 4 , IL 5 , IL 10 , and IL 13 each regulate distinct aspects of the granulomatous inflammatory response , IL 13 was identified as the primary mediator of liver fibrosis . Thus , elucidating the mechanisms that regulate the production and function of IL 13 has become an intensive area of research . IL 13 signaling is mediated by the type 2 IL 4 receptor , which consists of the IL 4R alpha and IL 13R alpha 1 chains . however , another IL 13 binding chain , IL 13R alpha 2 , appears to strongly inhibit the activity of IL 13 . animals deficient in IL 13R alpha 2 fail to downmodulate granuloma formation in the chronic phase of infection . They also develop severe IL 13 dependent fibrosis and portal hypertension and quickly succumb …

Comparison of peripheral blood leukocyte kinetics after live escherichia coli , endotoxin , or interleukin 1 alpha administration. (1993 Aug)
comparison of peripheral blood leukocyte kinetics after live escherichia coli , endotoxin , or interleukin 1 alpha administration . studies using a novel interleukin 1 receptor antagonist . objective : This study was undertaken to evaluate whether hematologic and immunologic effects observed after bacteremia and endotoxemia in the host could be replicated by administration of recombinant human interleukin 1 alpha ( IL 1 alpha ) in a primate model . furthermore , to determine whether endogenously produced interleukin 1 ( IL 1 ) contributes to the changes observed during endotoxemia or gram negative septic shock , a specific IL 1 receptor antagonist ( IL 1 ra ) was administered . summary background DATA : The lipopolysaccharide ( LPS ) component of the outer membrane of gram negative bacteria initiates a constellation of metabolic and immunologic host responses . IL 1 , a macrophage derived cytokine , acts as a key mediator in the host response to infection and inflammation . methods : baboons were randomly assigned to receive either recombinant human IL 1 alpha , LPS , or live escherichia coli both with or without concomitant administration of IL 1ra . blood was collected hourly and analyzed using flow cytometric techniques . results : Both endotoxemia and live E . coli bacteremia induced an acute granulocytopenia ; however , the granulocytopenia gradually resolved in the endotoxemic group , but was sustained in the bacteremic group . An early lymphopenia and monocytopenia was elicited by LPS or E . coli and …

Tissue interleukin 1 and interleukin 1 receptor antagonist expression in enterocolitis in resistant and susceptible rats. (1994 May)
tissue interleukin 1 and interleukin 1 receptor antagonist expression in enterocolitis in resistant and susceptible rats . background / AIMS : subserosal injection of purified group A streptococcal peptidoglycan polysaccharide ( PG APS ) induces chronic relapsing granulomatous enterocolitis and systemic inflammation in susceptible inbred lewis rats but only transient intestinal injury in buffalo and fischer rats . cecal interleukin 1 ( IL 1 ) and IL 1 receptor antagonist ( IL 1ra ) expression was measured in inbred rats displaying differential susceptibility to experimental enterocolitis . methods : The ileum and cecum of lewis , buffalo , and fischer rats were subserosally injected with purified PG APS or albumin . IL 1 and IL 1ra messenger RNA ( mRNA ) and protein ( IL 1 only ) were measured 1 or 27 days later . PG APS injected lewis rats were treated with recombinant human IL 1ra . kinetics of IL 1 and IL 1ra mRNA expression were studied in peritoneal cells . results : All rats strains developed acute inflammation with increased cecal concentrations of IL 1 beta and IL 1ra mRNA . lewis rats developed chronic enterocolitis and had higher IL 1 and IL 1ra mRNA tissue levels than buffalo or fischer rats , which displayed no chronic inflammation . IL 1 beta and IL 1ra were produced by submucosal granulomas and correlated with inflammation . IL 1 alpha protein levels paralleled IL 1 beta mRNA expression . IL 1ra treatment attenuated acute and chronic enterocolitis , …

Signaling by IL 12 and IL 23 and the immunoregulatory roles of stat4. (2004 Nov)
signaling by IL 12 and IL 23 and the immunoregulatory roles of stat4 . produced in response to a variety of pathogenic organisms , interleukin ( IL ) 12 and IL 23 are key immunoregulatory cytokines that coordinate innate and adaptive immune responses . these dimeric cytokines share a subunit , designated p40 , and bind to a common receptor chain , IL 12R beta 1 . The receptor for IL 12 is composed of IL 12R beta 1 and IL 12R beta 2 , whereas IL 23 binds to a receptor composed of IL 12R beta 1 and IL 23R . Both cytokines activate the janus kinases Tyk2 and Jak2 , the transcription factor signal transducer and activator of transcription 4 ( stat4 ) , as well as other stats . A major action of IL 12 is to promote the differentiation of naive CD4 T cells into T helper ( Th ) 1 cells , which produce interferon ( IFN ) gamma , and deficiency of IL 12 , IL 12R subunits or stat4 is similar in many respects . In contrast , IL 23 promotes end stage inflammation . targeting IL 12 , IL 23 , and their downstream signaling elements would therefore be logical strategies for the treatment of immune mediated diseases .

Pathogenic role of interleukin 6 in the development of sepsis. (2003 May)
pathogenic role of interleukin 6 in the development of sepsis . Part II : significance of anti interleukin 6 and anti soluble interleukin 6 receptor alpha antibodies in a standardized murine contact burn model . objective : The in vivo effects of anti interleukin 6 ( anti IL 6 ) and anti interleukin 6 alpha receptor ( anti IL 6R ) monoclonal antibodies on immune response and survival rate of a burn with subsequent infection were assessed . subjects : Ten week old C 57 BL / 6J mice received a standardized contact burn ; 48 hrs later endotoxin ( LPS ) was injected intraperitoneally to induce systemic inflammation . Ten different groups were studied . groups I IV sustained a burn and / or a LPS stimulus but did not receive any anti cytokines and served as controls . treatment groups V X sustained the same injuries but also received anti IL 6 and anti IL 6R intravenously either before or after the LPS stimulus . In a further part of the study , a lethal dose of LPS was injected ( LPS LD ( 100 ) group ) followed by an injection of anti IL 6 antibody and / or anti IL 6R antibody . measurements : serum concentrations of IL 6 , tumor necrosis factor ( TNF ) alpha , interferon ( IFN ) gamma , and white blood cell and platelet counts were determined , and the survival rate over a 2 wk period was assessed …

Expression of a single chain human interleukin 12 gene in transgenic tobacco plants and functional studies. (2004 Mar)
expression of a single chain human interleukin 12 gene in transgenic tobacco plants and functional studies . interleukin 12 ( IL 12 ) is a key heterodimeric cytokine produced by a variety of antigen presenting cells , including dendritic cells , macrophages , and B cells . It displays a potent array of biological activities affecting natural killer ( NK ) and T cells . these activities include promotion of cell mediated or type 1 T helper cell responses ( Th1 ) . Due to that property , IL 12 has been employed in cancer immunotherapy , in mouse models of infectious diseases and in airway inflammation , and it may also have utility as a vaccine adjuvant . transgenic plants are being used in many laboratories around the world for the production of therapeutically valuable proteins and as vehicles for oral vaccines . Here we present the expression of a single chain human interleukin 12 in transgenic tobacco plants . The biological activity of plant produced IL 12 was determined by interferon gamma ( IFN gamma ) production by natural killer ( NK ) cells , and the level of production was comparable to that obtained with commercially available recombinant IL 12 . The potential use of this recombinant protein is discussed .

Interleukin 1 receptor antagonist suppresses experimental autoimmune encephalomyelitis ( EAE ) in rats by influencing the activation and proliferation of … (1998 Jul)
interleukin 1 receptor antagonist suppresses experimental autoimmune encephalomyelitis ( EAE ) in rats by influencing the activation and proliferation of encephalitogenic cells . considering the role of pleiotropic interleukin 1 ( IL 1 ) in inflammation and autoimmunity , studies were designed to examine whether specific blockade of IL 1 may influence these processes in the CNS . although the role of CD4 T cells in eliciting clinical signs of experimental autoimmune encephalomyelitis ( EAE ) has been unequivocally demonstrated , the exact mechanism by which encephalitogenic cells initiate disease process and bring about clinical signs still remains to be defined . We have evaluated the effect of human recombinant interleukin 1 receptor antagonist ( IL 1Ra ) in vivo on the course of actively induced EAE in highly susceptible Dark agouti ( DA ) rats . The rats which were treated during the induction phase of disease ( days 0 6 ) with IL 1Ra ( 350 microg / rat / day ) developed milder signs of EAE , when compared to saline treated control animals immunized with encephalitogen , which developed severe single episode disease . The transfer of lymph node cells ( LNC ) isolated from MBP primed DA rats and stimulated in vitro with MBP and ConA to naive syngeneic animals resulted in the development of EAE in all recipients . however , rats injected with LNC that have been stimulated in vitro in the presence of IL 1Ra ( 10 microg / ml ) developed …

Human neutrophils express the high affinity receptor for immunoglobulin E ( Fc epsilon RI ) : role in asthma. (2001 Apr)
human neutrophils express the high affinity receptor for immunoglobulin E ( Fc epsilon RI ) : role in asthma . polymorphonuclear neutrophils ( PMNs ) are important effector cells in host defense and the inflammatory response to antigen . The involvement of PMNs in inflammation is mediated mainly by the Fc receptor family , including IgE receptors . recently , PMNs were shown to express two IgE receptors ( CD23 / Fc epsilon RII and galectin 3 ) . In allergic diseases , the dominant role of IgE has been mainly ascribed to its high affinity receptor , Fc epsilon RI . We have examined the expression of Fc epsilon RI by PMNS : mRNA and cell surface expression of Fc epsilon RI alpha chain was identified on PMNs from asthmatic subjects . furthermore , preincubation with human IgE Fc fragment blocks completely the binding of anti Fc epsilon RI alpha chain ( mab15 1 ) to human PMNS : conversely , preincubation of PMNs with mab15 1 inhibits significantly the binding of IgE Fc fragment to PMNs , indicating that IgE bound to the cell surface of PMNs mainly via the Fc epsilon RI . peripheral blood and bronchoalveolar lavage ( BAL ) PMNs from asthmatic subjects also express intracellular Fc epsilon RI alpha and beta chain immunoreactivity . engagement of Fc epsilon RI induces the release of IL 8 by PMNS : collectively , these observations provide new evidence that PMNs express the Fc epsilon RI and suggest …

Interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni. (2001 Apr)
interleukin 12 and antigen independently induce substance P receptor expression in T cells in murine schistosomiasis mansoni . substance P ( SP ) regulates interferon gamma ( IFN gamma ) production through interaction with the SP receptor NK1 ( SPr ) on T cells at sites of inflammation . using murine schistosomiasis , we evaluated whether SPr expression was subject to immunoregulation . splenocytes from schistosome infected mice cultured for or 18 h did not express SPr , as determined by quantitative polymerase chain reaction assay . however , exposure to schistosome egg antigen ( SEA ) for or 4 h induced strong receptor expression . experiments using splenocytes fractionated with antibody coupled , paramagnetic beads showed that induction localized exclusively to T cells . receptor protein expression was confirmed with western blot . interleukin 12 ( IL 12 ) also induced strong T cell SPr expression . Both SEA and IL 12 remained strong inducers of T cell SPr in lymphocytes from the IL 12 ( p40 ) and IFN gamma R double knockout mouse , which suggested that SEA did not require IL 12 to induce SPr and that both worked independently of IFN gamma . splenocytes from wild type mice cultured with SEA and neutralizing anti IL 12 monoclonal antibody ( mAb ) also showed SPr induction . however , anti Ia mAb inhibited SEA induction of SPR : Thus , SPr is inducible on T cells . SEA induces SPr through interaction with T cell receptor …

Bile acid stimulated expression of the farnesoid X receptor enhances the immune response in barrett esophagus. (2008 Jun)
Bile acid stimulated expression of the farnesoid X receptor enhances the immune response in barrett esophagus . objectives : barrett s esophagus ( BE ) is a premalignant condition of the esophagus . It is a consequence of mucosal injury from chronic gastroesophageal reflux in which bile acids are an important toxic component . The farnesoid X receptor ( FXR ) is a nuclear receptor involved in the regulation of bile acid synthesis , transport , and absorption . FXR activation is also involved in the induction of the innate immune response . This suggests that FXR is involved in the pathogenesis and the inflammation seen in BE . methods : mRNA levels of FXR and the FXR regulated genes , ileal bile acid binding protein ( ibabp ) , small heterodimer partner ( SHP ) , and chemokines interleukin ( IL ) 8 and macrophage inflammatory protein 3 alpha ( MIP3 alpha ) , were determined by real time polymerase chain reaction ( RT PCR ) . protein expression was determined by immunohistochemistry . results : FXR was not expressed in squamous epithelium of healthy subjects ( N 7 ) , but was present in both squamous and columnar epithelium of BE patients . compared to the squamous epithelium of BE patients , their columnar epithelium displayed a 2 . 3 fold ( P 0 . 02 ) increase in FXR mRNA . Also , ibabp ( 2 . 2 fold ; P 0 . 0029 ) , SHP …

Cytokine gene expression in aortic adventitial inflammation associated with advanced atherosclerosis ( chronic periaortitis ). (1994 Dec)
cytokine gene expression in aortic adventitial inflammation associated with advanced atherosclerosis ( chronic periaortitis ) . AIMS : To determine whether aortic adventitial chronic inflammation associated with advanced atherosclerosis ( chronic periaortitis ) is associated with any detectable cytokine gene expression . methods : RNA was extracted from six fresh surgical specimens of atherosclertic aortic aneurysm wall showing a spectrum of chronic periaortitis . controls included four normal aortas and an HUT 78 T cell line . reverse transcriptase and the polymerase chain reaction ( PCR ) were used to amplify mRNA for interleukins 1 alpha ( IL 1 alpha ) , 2 ( IL 2 ) , 4 ( IL 4 ) , IL 2 receptor alpha ( IL 2R alpha ) , tumour necrosis factor alpha ( TNF alpha ) and gamma interferon ( IFN gamma ) with beta actin as an internal control . results : No TNF alpha mRNA was detected in any of the inflamed aortic tissue samples , in contrast to the aortic T lymphocytes propagated in culture in IL 2 conditioned medium ( aortic cultured T cells ) and peripheral blood mononuclear cells from these patients . In contrast , IFN gamma , IL 1 alpha , IL 2 , IL 2 receptor and IL 4 PCR products were detected for each inflamed aortic tissue RNA sample with IFN gamma mRNA expression increasing with increasing degrees of adventitial inflammation . Only beta actin mRNA was present in the normal aorta . conclusions : …

Cytokine gene expression during the development of graft coronary artery disease in mice. (1999 Dec)
cytokine gene expression during the development of graft coronary artery disease in mice . immunologic injury to heart allografts is an initial and essential event in the pathogenesis of graft coronary artery disease ( GAD ) . A variety of cytokines expressed in heart allografts modify both acute rejection and chronic inflammation , and could contribute to the development of GAD . The present study investigated the gene expression of interleukin ( IL ) 1beta , IL 2 , IL 4 , IL 6 , IL 10 , tumor necrosis factor ( TNF ) alpha , interferon ( IFN ) gamma , and Fas ligand in chronically rejecting DBA / 2 to B 10 . D2 mouse heart allografts at defined intervals of 7 , 14 , 28 , or 70 days after transplantation by semiquantitative reverse transcriptase polymerase chain reaction . GAD developed gradually , showing the highest value for mean intima / media ratio at day 70 . Fas ligand , and the Th1 cytokines IL 2 and IFN gamma , were vigorously induced in allografts at day 7 , when histology showed pronounced parenchymal rejection , and rapidly decreased by day 28 . however , the level of mRNA expression of Th2 cytokines , IL 6 and IL 10 , and other inflammatory cytokines , TNF alpha and IL 1beta , were still elevated on day 28 . The persistent expression of specific cytokines suggests an important role in chronic inflammation . Thus , a persistently high …

Polymorphism of the cytokine genes and IgA nephropathy. (2002 Feb)
polymorphism of the cytokine genes and IgA nephropathy . background : IgA nephropathy ( IgAN ) is a form of chronic glomerulonephritis of unknown etiology and pathogenesis . cytokine gene polymorphisms regulate cytokine production and play a role in immune and inflammatory responses ; these immunological responses thus are possibly involved in the etiology and pathogenesis of IgAN . methods : We studied by polymerase chain reaction ( PCR ) polymorphisms of important cytokine genes of inflammation interleukin 1 ( IL 1beta ) , tumor necrosis factor alpha ( TNF alpha ) , interleukin 6 ( IL 6 ) , and interleukin 1 receptor antagonist ( IL 1Ra ) in 167 patients with IgAN and 400 healthy blood donor controls . IgAN patients had been followed up for 6 to 17 ( median 11 ) years from renal biopsy . results : carriage of the IL 1beta allele 2 ( il1beta2 ) or IL 1Ra allele 2 ( il1rn 2 ) was associated with an increased risk of IgAN . these alleles were highly linked and the odds ratio ( OR ) of IgAN for carriage of both alleles was 1 . 8 ( 95 confidence interval 1 . 2 to 2 . 6 ; P 0 . 002 ) . carriage of the TNF alpha allele 2 ( TNF2 ) was associated with a decreased risk of IgAN ( OR 0 . 5 , range 0 . 3 to 0 . 7 ; P 0 . 001 ) . …

Concordant and discordant interleukin 1 mediated signaling in lung fibroblast thy 1 subpopulations. (2002 May)
concordant and discordant interleukin 1 mediated signaling in lung fibroblast thy 1 subpopulations . following lung injury or inflammation , fibroblasts mediate either restorative repair or disordered remodeling . interleukin ( IL ) 1beta is a key mediator in the transition from injury / inflammation to tissue remodeling , in part through its regulation of platelet derived growth factor alpha receptor ( pdgfalphar ) . based on prior demonstration of differential pdgfalphar expression , we hypothesized that subpopulations of fibroblasts would have heterogeneous responses to IL 1 . We report that IL 1beta significantly increases expression of pdgfalphar in Thy 1 , but not Thy 1 fibroblasts . higher baseline expression of pdgfalphar in Thy 1 fibroblasts is partially abrogated by IL 1 receptor antagonist . there are no differences in IL 1beta binding , as determined by flow cytometry , or in the presence of the type I IL 1 receptor ( IL 1RtI ) or its associated protein ( IL 1racp ) by immunoblotting . IL 1beta induces DNA binding of both nuclear factor kappab ( NF kappab ) and caatt enhancer binding protein ( C / EBP ) , and activation of p38 mitogen activated protein kinase in both subpopulations . however , IL 1beta induced proliferation and expression of IL 6 are significantly higher in Thy 1 fibroblasts . heterogeneous responses to IL 1beta despite equivalent presence of both proximal and distal signaling components indicates that parallel signaling pathways are activated selectively in Thy 1 cells …

The interleukin 1 system : receptors , ligands , and ICE in the brain and their involvement in the fever … (1998 Jul)
The interleukin 1 system : receptors , ligands , and ICE in the brain and their involvement in the fever response . The ligands and the receptors of the interleukin 1 ( IL 1 ) system constitute a highly inducible set of proteins whose expression in infection and inflammation is of key importance in the host defense . The IL 1 system participates in the stimulation of the immune system , the neuroendocrine system , and the neuroimmune system . The major soluble and secreted agonist of the system , IL 1 beta , has been studied by mutational and transgenic approaches . furthermore , involvement of the signal transducing type I IL 1 receptor ( IL 1RI ) , in fever and other responses , has been studied by null mutation technique . We describe the inducible expression of the two agonists , IL 1 alpha ( 31 kDa and 17 kDa ) and IL 1 beta ( 17 kDa ) and of the IL 1 receptor subtypes IL 1RI and IL 1RII in the brain and in the adrenals ( as well as in the pituitary cell line att20 ) . We also describe an additional member of the IL 1 family : the IL 1 receptor antagonist ( IL 1ra ) , an endogenous antagonist to IL 1 alpha and IL 1 beta . furthermore , the IL 1 beta converting enzyme ( ICE ) and its differential regulation and expression in brain and adrenals is also …

IL 1 alpha stimulates the formation of osteoclast like cells by increasing M CSF and PGE2 production and decreasing OPG … (2005 May)
IL 1 alpha stimulates the formation of osteoclast like cells by increasing M CSF and PGE2 production and decreasing OPG production by osteoblasts . interleukin 1alpha ( IL 1alpha ) is one of the most potent bone resorbing factors involved in the bone loss that is associated with inflammation . We examined the effect of the inflammatory mediator IL 1alpha on the expression of macrophage colony stimulating factor ( M CSF ) , osteoprotegerin ( OPG ) , and prostaglandin E2 ( PGE2 ) in rat osteoblasts , and the indirect effect of IL 1alpha on the formation of osteoclast like cells . osteoblasts were cultured in alpha minimum essential medium containing 10 fetal bovine serum with or without 100 units / ml of IL 1alpha for up to 14 days . The gene and protein expression of M CSF and OPG were estimated by determining mRNA levels using the real time polymerase chain reaction and protein levels using western blot analysis . PGE2 expression was determined using an enzyme linked immunosorbent assay . The formation of osteoclast like cells was estimated using tartrate resistant acid phosphatase ( TRAP ) staining of osteoclast precursors in culture with conditioned medium from IL 1alpha treated osteoblasts and the soluble receptor activator of NF kappab ligand ( rankl ) . M CSF and PGE2 expression in osteoblasts increased markedly in cells cultured with IL 1alpha , whereas OPG expression decreased . The conditioned medium containing M CSF and PGE2 produced by IL 1alpha …

The human interleukin 1 alpha gene is located on the long arm of chromosome 2 at band q13. (1989 Feb)
The human interleukin 1 alpha gene is located on the long arm of chromosome 2 at band q13 . interleukin 1 alpha ( IL 1 alpha ) and interleukin 1 beta ( IL 1 beta ) are two biochemically distinct , but distantly related , polypeptidic cytokines that play a key role in inflammation , immunologic reactions , and tissue repair . recently , it has been shown that IL 1 alpha is identical to hematopoietin 1 , which was described as a hematopoietic growth factor acting on early progenitor cells in synergy with other hematopoietic growth factors . In this report we discuss our use of in situ hybridization on human prometaphase cells with a human IL 1 alpha cDNA probe to localize the human IL 1 alpha gene on the proximal part of the long arm of chromosome 2 at band q13 , in the same chromosomal region as the IL 1 beta gene .

Characterization of the human interleukin 1 receptor on human polymorphonuclear leukocytes. (1988 Sep)
characterization of the human interleukin 1 receptor on human polymorphonuclear leukocytes . interleukin 1 ( IL 1 ) is a mediator of inflammation with multiple proinflammatory and immunologic enhancing activities . human polymorphonuclear leukocytes ( PMN ) also play a major role in the inflammatory response . We have found that PMN possess a single type of high affinity receptor for human recombinant ( r ) IL 1 alpha with an apparent dissociation constant of 0 . 28 nM . approximately 700 receptors are present per cell . binding is rapid with 50 of maximal binding occurring within 20 min at 4 degrees C . internalization of the receptor occurs within 25 min after shifting the cells to 37 degrees C . The receptor exhibits an apparent molecular weight of approximately 60 70 kDa . electron microscopic autoradiography studies reveal that the 125I rIL 1 alpha localized in the nucleus within 180 min after shifting cells to 37 degrees C . The accumulation of relatively high levels of 125I rIL 1 alpha in the nucleus is consistent with earlier observations on the nuclear localization of IL 1 in T lymphocytes . The possibility that IL 1 may exert a direct action in the nucleus remains to be determined .

Autoregulation of interleukin 1 production. (1989 May)
autoregulation of interleukin 1 production . interleukin 1 ( IL 1 ) alpha and beta are distinct cytokines with a common receptor on target cells . Both have been implicated in immunity , inflammation and connective tissue metabolism . their production is stimulated by microbial products and also by other cytokines derived from accessory cells and lymphocytes . following reports that IL 1 can stimulate its own production , we have tested the effects of recombinant IL 1 on the synthesis and release of IL 1 alpha and beta by human blood mononuclear cells ( MNC ) . We confirmed that autoinduction occurs but report also the novel finding that this effect is very concentration dependent . At some concentrations within the range found in vivo , recombinant IL 1 not only failed to stimulate further IL 1 production but also inhibited the background level of synthesis in 20 h MNC cultures . The negative feedback appears unrelated to prostaglandin E2 and interferon gamma levels and could not be reproduced by adding transforming growth factor beta . This previously unrecognized autoregulation may be relevant to clinical diseases associated with pathogenic over production of IL 1 .

IL 13 signal transduction in human monocytes : phosphorylation of receptor components , association with Jaks , and phosphorylation / … (2002 Sep)
IL 13 signal transduction in human monocytes : phosphorylation of receptor components , association with Jaks , and phosphorylation / activation of stats . interleukin ( IL ) 13 regulates monocyte function and is a potent stimulator of 15 lipoxygenase expression . In different cell types , the functional IL 13 receptor complex can be comprised of variable protein components and has not been thoroughly examined in human monocytes . Here , we identify the receptor components and upstream signaling events initiated by IL 13 in primary human blood monocytes . The expression , phosphorylation and associated Jak kinases of the known , variable receptor components , IL 4R ( alpha ) , IL 2rgammac , IL 13R ( alpha ) 1 and IL 13R ( alpha ) 2 , were examined . We determined that IL 4R ( alpha ) and il13r ( alpha ) 1 are phosphorylated upon exposure to IL 13 . although IL 2rgammac is also expressed , it is not phosphorylated upon exposure to IL 13 . evaluation of the presence of IL 13R ( alpha ) 2 failed to reveal significant mRNA or protein expression . earlier , our laboratory showed that IL 13 induced the phosphorylation of Jak2 and Tyk2 in monocytes and that expression of both Jaks was essential for downstream signaling by IL 13 . Here , we report that Jak2 is associated with IL 4R ( alpha ) , and Tyk2 is associated with the IL 13R ( alpha ) …