Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One of the factors that contributes to the pathogenesis of acne is Propionibacterium acnes; yet, the molecular mechanism by which P. acnes induces inflammation is not known. Recent studies have demonstrated that microbial agents trigger cytokine responses via Toll-like receptors (TLRs). We investigated whether TLR2 mediates P. acnes-induced cytokine production in acne. Transfection of TLR2 into a nonresponsive cell line was sufficient for NF-kappa B activation in response to P. acnes. In addition, peritoneal macrophages from wild-type, TLR6 knockout, and TLR1 knockout mice, but not TLR2 knockout mice, produced IL-6 in response to P. acnes. P. acnes also induced activation of IL-12 p40 promoter activity via TLR2. Furthermore, P. acnes induced IL-12 and IL-8 protein production by primary human monocytes and this cytokine production was inhibited by anti-TLR2 blocking Ab. Finally, in acne lesions, TLR2 was expressed on the cell surface of macrophages surrounding pilosebaceous follicles. These data suggest that P. acnes triggers inflammatory cytokine responses in acne by activation of TLR2. As such, TLR2 may provide a novel target for treatment of this common skin disease.
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PMID:Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. 1213 81

Human granulocytic ehrlichiosis (HGE), a tick-borne zoonosis, is caused by an obligatory intragranulocytic bacterium, the HGE agent, a strain of Anaplasma phagocytophila. The equine model of HGE is considered valuable in understanding pathogenic and immune mechanisms of HGE. In the present study, cytokine mRNA expression by peripheral blood leukocytes (PBLs) in horses was examined during the course of infection by intravenous inoculation of A. phagocytophila or by allowing feeding by infected ticks. The p44 genes encoding the major outer membrane protein P44s of A. phagocytophila were detected by PCR in PBLs of all four horses from 4 to 20 days postexposure. During the 20-day infection period, interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNF-alpha) mRNA expression was upregulated in PBLs of all four horses, and IL-8 mRNA expression was upregulated in three horses. Gamma interferon, IL-10, and IL-12 p35 mRNAs were weakly expressed in only one horse each. IL-2, IL-4, IL-6, and IL-12 p40 mRNA expression, however, could not be detected in the PBLs of any of the four horses. These results suggest that IL-1beta, TNF-alpha, and IL-8 generation during A. phagocytophila infection has a primary role in HGE pathogenesis and immunomodulation.
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PMID:Cytokine gene expression by peripheral blood leukocytes in horses experimentally infected with Anaplasma phagocytophila. 1220 63

A rapid multi-probe ribonuclease protection assay (RPA) was developed to quantitate equine-specific cytokine mRNA levels in activated equine monocyte-derived macrophages (EMDM) and equine peripheral blood mononuclear cells (EPBMC). Eleven template plasmids specific to 10 equine cytokine genes and the beta-actin gene were generated from which radiolabeled anti-sense RNA probes were produced. The multi-probe RPA simultaneously quantitated mRNA levels of equine IL-1alpha, IL-1beta, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, IFN-gamma, TGF-1beta and TNF-alpha in EPBMC and EMDM with coefficients of variation as low as 0.03-0.08 (3-8%) when normalized to beta-actin expression. This sensitive and rapid assay provides a valuable tool for studies of equine immune responses.
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PMID:Simultaneous quantitation of equine cytokine mRNAs using a multi-probe ribonuclease protection assay. 1250 49

An experimental model was used to investigate mRNA cytokine profiles in bronchoalvolar cells (BALC) from piglets, infected in utero with porcine reproductive and respiratory syndrome virus (PRRSV). The BALC's were analyzed for the cytokines TNF-alpha, IFN-gamma, IL-8, IL-10, and IL-12(p40) by real-time TaqMan polymerase chain reaction in 2-, 4-, and 6-week-old piglets, respectively. High levels of IFN-gamma mRNA was detected in all piglets, while IL-10 was upregulated in 2-week-old piglets, was at normal levels in 4-week-old piglets, and elevated again in 6-week-old piglets. IL-12 was weakly elevated in all three age groups. Virus was reduced by 50% in 4-week-old piglets and cleared by 6 weeks of age. The sustained expression of IFNgamma and reduction of IL-10 production indicate an important role for these cytokines in immunity to PRRSV.
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PMID:Cytokine mRNA profiles in bronchoalveolar cells of piglets experimentally infected in utero with porcine reproductive and respiratory syndrome virus: association of sustained expression of IFN-gamma and IL-10 after viral clearance. 1251 26

The early consequences of Helicobacter pylori infection and the role of bacterial virulence determinants in disease outcome remain to be established. The present study sought to measure the development of host inflammatory and immune responses and their relationship to the putative bacterial virulence factors cag pathogenicity island (cagPAI), vacA allele, and oipA in combination with bacterial colonization density in a feline model of the early stages of H. pylori infection. Gastric tissues obtained from infected and uninfected cats were evaluated for H. pylori ureB, cagPAI, vacA allele, and oipA and colonization density (urease, histology, and real-time PCR). Inflammation was assessed by measuring mRNA upregulation of gamma interferon (IFN-gamma), interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, IL-8, IL-10, and IL-12 p40 and histopathology. The mucosal immune response was characterized by morphometric analysis of lymphoid follicles and by differentiating lymphocyte populations with antibodies against surface markers. Infecting H. pylori strains were positive for vacAs1 but lacked cagPAI and an active oipA gene. Colonization density was uniform throughout the stomach. Upregulation of IFN-gamma, IL-1 alpha, IL-1 beta, and IL-8 and increased severity of inflammatory infiltrates and fibrosis were observed in infected cats. The median number and total area of lymphoid aggregates were 5 and 10 times greater, respectively, in the stomachs of infected than uninfected cats. Secondary lymphoid follicles in uninfected cats were rare and positive for BLA.36 and B220 but negative for CD3 and CD79 alpha, whereas in infected cats they were frequent and positive for BLA.36, CD79 alpha, and CD3 but negative for B220. Upregulation of IFN-gamma, IL-1 alpha, IL-1 beta, and IL-8 and marked hyperplasia of secondary lymphoid follicles are early consequences of H. pylori infection in cats. The response appears to be similar to that of infected people, particularly children, can develop independently of the pathogenicity factors cagPAI and oipA, and is not correlated with the degree of colonization density or urease activity.
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PMID:Quantitative evaluation of inflammatory and immune responses in the early stages of chronic Helicobacter pylori infection. 1270 44

Parasite Ag-specific T cell unresponsiveness and diminished IFN-gamma production are immunologic hallmarks of patent infection with lymph-dwelling filarial nematodes. Although this diminished responsiveness is directed primarily against the intravascular microfilarial (MF) parasite stage and mediated in part by reduced APC function, the mechanisms involved are not fully understood. In this report, we demonstrate that human dendritic cells (DC) exposed to live MF up-regulate both the cell surface and gene expression of CD54 (ICAM-1). Moreover, live MF result in a 3-fold increase in DC death compared with MF-unexposed DC, primarily due to apoptosis. Notably, microarray and real-time RT-PCR data indicate that live MF concurrently up-regulate mRNA expression of proinflammatory molecules such as IL-8, RANTES, IL-1alpha, TNF-alpha, and IL-beta in DC, the presence of which is also detected at the protein level, while inhibiting the production of IL-12 (p40 and p70) and IL-10. Soluble excretory-secretory products from live MF diminished IL-12 and IL-10 production and induced DC death, although to a lesser degree. Moreover, exposure of DC to live MF resulted in a decrease in the ability of DC to promote CD4(+) T cell production of IFN-gamma and IL-5. Our findings clearly suggest that the interaction between live MF and DC is complex but contributes to the hyporesponsiveness and parasite persistence associated with the MF(+) state in the infected human. These data further suggest that MF induce an orchestrated response in APC that leads to a diminished capacity to function appropriately, which in turn has significant consequences for CD4(+) T cells.
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PMID:Brugia malayi microfilariae induce cell death in human dendritic cells, inhibit their ability to make IL-12 and IL-10, and reduce their capacity to activate CD4+ T cells. 1290 98

Nitric oxide (NO) has an established role in the defense against bacterial infections and exerts multiple modulatory activities on both inflammatory and immune responses. However, the relevance of NO on dendritic cell (DC) functions has been poorly investigated. In this study, we found that addition of the NO donor S-nitrosoglutathione (GSNO) to monocyte-derived DCs matured by lipopolysaccharide (LPS) or soluble CD40 ligand led to a decreased capacity to activate naive allogeneic T cells but a more prominent Th1 polarization, with increased interferon-gamma (IFN-gamma) secretion and reduced interleukin-5 (IL-5) release. The presence of GSNO during maturation of DCs caused a reduced expression of surface CD86, whereas CD80, CD83, and MHC molecule expression was not affected. Moreover, GSNO induced a dose-dependent decrease of IL-10 and enhancement of tumor necrosis factor-alpha (TNF-alpha) release from mature DCs. In parallel, a marked reduced production of IL-12 p40 subunit but no significant perturbation of the bioactive IL-12 p70 production was observed. Finally, GSNO significantly reduced the release of IP-10/CXCL10 and RANTES/CCL5 but not IL-8/CXCL8 by mature DCs. Although GSNO can strengthen the capacity of mature DCs to induce type 1 polarization of T lymphocytes, our data suggest that it elicits distinct anti-inflammatory functions, eventually reducing T lymphocyte proliferation and recruitment.
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PMID:Regulatory role of nitric oxide on monocyte-derived dendritic cell functions. 1367 30

Human polymorphonuclear leukocytes (PMNs or neutrophils) kill invading microorganisms with reactive oxygen species (ROS) and cytotoxic granule components. PMNs from individuals with X-linked chronic granulomatous disease (XCGD) do not produce ROS, thereby rendering these individuals more susceptible to infection. In addition, XCGD patients develop tissue granulomas that obstruct vital organs, the mechanism(s) for which are unknown. To gain insight into the molecular processes that contribute to the pathophysiology of XCGD, including formation of granulomas, we compared global gene expression in PMNs from XCGD patients and healthy control individuals. Genes encoding mediators of inflammation and host defense, including CD11c, CD14, CD54, FcgammaR1, FcalphaR, CD120b, TLR5, IL-4R, CCR1, p47(phox), p40(phox), IL-8, CXCL1, Nramp1, and calgranulins A and B, were up-regulated constitutively in unstimulated XCGD patient PMNs. By comparing transcript levels in normal and XCGD PMNs after phagocytosis, we discovered 206 genes whose expression changed in the presence and the absence of ROS, respectively. Notably, altered Bcl2-associated X protein synthesis accompanied defective neutrophil apoptosis in XCGD patients. We hypothesize that granuloma formation in XCGD patients reflects both increased proinflammatory activity and defective PMN apoptosis, and we conclude that ROS contribute directly or indirectly to the resolution of the inflammatory response by influencing PMN gene transcription.
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PMID:Gene expression profiling provides insight into the pathophysiology of chronic granulomatous disease. 1468 76

The NADPH oxidase 1 (Nox1) is a gp91(phox) homologue preferentially expressed in the colon. We have established primary cultures of guinea pig large intestinal epithelial cells giving 90% purity of surface mucous cells. These cells spontaneously released superoxide anion (O(2)(-)) of 160 nmol/mg protein/h and expressed the Nox1, p22(phox), p67(phox), and Rac1 mRNAs, but not the gp91(phox), Nox4, p47(phox), p40(phox), and Rac2 mRNAs. They also expressed novel homologues of p47(phox) and p67(phox) (p41(nox) and p51(nox), respectively). Human colon cancer cell lines (T84 and Caco2 cells) expressed the Nox1, p22(phox), p51(nox), and Rac1 mRNAs, but not the other NADPH component mRNAs, and secreted only small amounts of O(2)(-) (<2 nmol/mg protein/h). Cotransfection of p41(nox) and p51(nox) cDNAs in T84 cells enhanced PMA-stimulated O(2)(-) release 5-fold. Treatment of the transfected T84 cells with recombinant flagellin (rFliC) from Salmonella enteritidis further augmented the O(2)(-) release in association with the induction of Nox1 protein. The enhanced O(2)(-) production by cotransfection of p41(nox) and p51(nox) vectors further augmented the rFliC-stimulated IL-8 release from T84 cells. T84 cells expressed the Toll-like receptor 5, and rFliC rapidly phosphorylated TGF-beta-activated kinase 1 and TGF-beta-activated kinase 1-binding protein 1. A potent inhibitor for NF-kappaB (pyrrolidine dithiocarbamate) significantly blocked the rFliC-primed increase in O(2)(-) production and induction of Nox1 protein. These results suggest that p41(nox) and p51(nox) are involved in the Nox1 activation in surface mucous cells of the colon, and besides that, epithelial cells discern pathogenicities among bacteria to appropriately operate Nox1 for the host defense.
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PMID:Role of nicotinamide adenine dinucleotide phosphate oxidase 1 in oxidative burst response to Toll-like receptor 5 signaling in large intestinal epithelial cells. 1497 10

Human T lymphotrophic virus type-I (HTLV-I), a human retrovirus, infects CD4(+) lymphocytes and is thought to modify their function and a possible association with pulmonary diseases has also been suggested. However, little is known about the influence of HTLV-I on diffuse pan-bronchiolitis (DPB), a chronic inflammatory lung disease with infiltration of lymphocytes and hyperplasia of the bronchus-associated lymphoid tissue. In this study, 35 DPB patients with and without HTLV-I infection were examined. HTLV-I positive DPB patients were likely to have a larger affected area with lower FEV(1). The CD3(+)/CD25(+) lymphocyte percentage was significantly higher in the BALF of HTLV-I positive patients than in negative patients. MIP-1 alpha, IP-10 and levels in BALF were also significantly higher in HTLV-I positive patients than in negative patients. The levels of MCP-1 and IL-8 were not significantly different. In HTLV-I positive patients, the MIP-1 alpha and IP-10 levels showed a significant positive correlation with the percentage of CD3(+)/CD25 lymphocytes. BALF cells of all HTLV-I positive DPB patients showed expression of p40(tax) mRNA. We suggest that HTLV-I infection may modify DPB pathogenesis via activation of T cells. We also found that the frequency of ATL development in HTLV-I positive DPB patients was significantly higher than in all HTLV-I positive patients (OR = 8.22, 95% CI = 2.61-25.9, P < 0.01). The levels of TGF-beta in patients who developed ATL were significantly lower than in patients who did not develop ATL. Sensitivity and specificity were 80% and 85.7%, respectively (cut-off = 20 pg/ml). We also propose that these features should be taken into consideration in the treatment of DPB in HTLV-I infected individuals.
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PMID:Influence of human T lymphotrophic virus type I on diffuse pan-bronchiolitis. 1514 54


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