Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022568 (keratitis)
 5,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Herpetic stromal keratitis (HSK) appears to represent an immunopathologic response in the cornea of the eye to HSV-1. T cells of the CD4+ subset were shown to be involved in the mediation of HSK, but how they subserve an immunopathologic role is uncertain. In the present report, we have isolated cells from eyes in the active phase of HSK and studied their cytokine profile after culture in vitro or stimulation with Ag or nonspecific mitogens. Inflammatory cells recovered from eyes consist of polymorphonuclear leukocytes, macrophages, and lymphocytes. As reported before, all the lymphocyte recovered were of the CD4+ phenotype. After stimulation in vitro with Ag or mitogen the cytokines IL-2, IFN-gamma, and TNF-alpha/beta were produced, but not the cytokines IL-4 and IL-10. Thus, on the basis of cytokine profile, ocular lymphocytes were identified as Th1 cells. Ocular cells were also stimulated with PMA and shown to produce IL-1. The results were discussed in terms of the possible means by which the Th1 cells induce tissue damage in HSK as well as in terms of the possible means by which a preferential accumulation of Th1 cell occurs in the eye.
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PMID:Predominance of Th1 cells in ocular tissues during herpetic stromal keratitis. 135 34

HSV-1 topical infection on the murine cornea can induce herpetic stromal keratitis (HSK), a T cell-mediated inflammatory response that results in blindness. To begin to decipher the molecular interactions involved in this infection, extracts of infected corneas were assayed for the presence of seven different cytokines by ELISA. The most prominent cytokines detected were IL-1 alpha and IL-6. Both were elevated by day 2 after infection, reached peak levels of 82 and 538 pg/cornea, respectively, at day 10, and then diminished over the next 10 days. In contrast, TNF-alpha concentrations were not elevated over that seen in uninfected corneas at any time during the 20-day observation period. IFN-gamma and granulocyte-macrophage CSF corneal concentrations were below the sensitivity of the assay. We investigated whether passive transfer of antibody to viral glycoprotein D, which prevents HSK, influenced the production of IL-1 alpha and IL-6. It was found that corneal concentrations of IL-1 alpha were reduced threefold and IL-6 was undetectable at day 10 in the antibody-treated hosts. The levels of IL-10 and IL-4 in uninfected control and antibody-treated hosts were also monitored. Neither of these two regulatory cytokines was associated with HSK development or effective antibody therapy. Naive corneas cultured in vitro spontaneously produced IL-1 and IL-6, indicating that cells resident in the cornea had the ability to synthesize these proinflammatory cytokines. Collectively, our results imply that IL-1 alpha and IL-6 may be important contributors to the development of HSK pathogenesis.
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PMID:Cytokine expression in vivo during murine herpetic stromal keratitis. Effect of protective antibody therapy. 839 96

Langerhans cells (LC) belong to the dendritic cell family and mediate Ag presentation in the cornea and ocular surface. Under normal physiological conditions, the central cornea is devoid of LC. Centripetal migration of LC plays a critical role in promoting immunoinflammatory responses in the eye including allograft rejection and herpetic keratitis. The molecular mechanisms responsible for ocular LC migration are poorly understood. To examine whether TNF-alpha mediates corneal LC migration and to establish the interaction of IL-1 and TNF-alpha in regulating LC migratory capacity, we utilized gene-targeted knockout mice lacking IL-1 receptor I (IL-1RI-/-), TNF receptor I (p55-/-), TNF receptor II (p75-/-), or both (p55-/-p75-/-). LC migration was induced by thermal cautery or cytokine injection and enumerated by an immunofluorescence assay. Migration of LC after cauterization and TNF-alpha injection was significantly depressed in both p55-/- and p75-/- mice. Similarly, in the first 72 h after intracorneal injection of IL-1alpha, LC migration was reduced in p55-/-, p75-/-, and p55-/-p75-/- mice. In contrast, injection of TNF-alpha in IL-1RI-/- mice led to normal migration of corneal LC indistinguishable from wild-type controls. These results suggest that the IL-1 induction of corneal LC migration is largely mediated by TNFR function, whereas TNF-alpha induction of LC migration is independent of IL-1RI activity. Moreover, the data suggest that both p55 and p75 signaling pathways are important in mediating LC migration in the cornea.
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PMID:TNF-alpha regulates corneal Langerhans cell migration. 1020 52

Pseudomonas aeruginosa can cause ulcerative bacterial keratitis or contact lens-induced acute red eye (CLARE) in humans. The present study used a mouse model of ocular infection and inflammation to examine the relationship between TNF-alpha and inflammation in the cornea in response to challenge with either a strain of P. aeruginosa causing keratitis or a CLARE strain. Constitutive TNF-alpha mRNA was detected in the epithelium, mainly towards the periphery. After infection with the keratitis-inducing strain (6294), TNF-alpha expression was elevated four-fold by 24 h post-challenge. No detectable induction of TNF-alpha mRNA was seen with CLARE strain (Paer1) challenge at any time point. The TNF-alpha protein production detected by ELISA showed a corresponding pattern to the mRNA expression, which also correlated with pathological changes. These results suggest that invasive strains of P. aeruginosa create greater pathological changes as a result of elevated TNF-alpha production, which contributes to inflammation during keratitis in vivo.
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PMID:TNF-alpha production in the cornea in response to Pseudomonas aeruginosa challenge. 1023 52

Cytokines are very important in the host defense system, and play a critical role in protection against bacterial and viral infections. Cytokines are also involved in the pathogenesis and development of symptoms in infections. In this article, Helicobacter pylori (H. pylori) infection as bacterial infection, and influenza virus infection, encephalomyocarditis virus (EMCV) infection, and herpes simplex virus (HSV) infection as viral infection are mentioned. In H. pylori infection, various chemokines, especially interleukin (IL)-8, induce inflammatory responses in the gastroduodenal mucosa. Furthermore, IL-6, IL-7, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma are involved in both protection and pathogenesis. In influenza virus infection, IFN-alpha/beta, IFN-gamma, and IL-6 play protective roles. In EMCV infection, IL-6 and TNF-alpha play important roles as a protective and exacerbative factor in acute myocarditis, respectively. Furthermore, in HSV infection, the production of inflammatory cytokines is closely correlated with the pathogenesis of herpetic keratitis, and IFN-gamma plays an important role in enhancing viral clearance from the cornea and trigeminal ganglions.
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PMID:Expression of cytokines in bacterial and viral infections and their biochemical aspects. 1073 41

The pathogenesis of pseudomonal keratitis was investigated by focusing on induction and activation of matrix metalloproteinases (MMPs) by pseudomonal virulence factors and proinflammatory cytokines. Corneal lesions and MMP induction in vivo were evaluated in rabbit corneas infected with a clinical isolate of Pseudomonas aeruginosa. Effects of pseudomonal virulence factors [elastase, alkaline protease, exotoxin A and lipopolysaccharide (LPS)], tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta on MMP induction and activation were further examined in vitro in rabbit corneal fibroblasts (RCF) and human fibrosarcoma (HT1080) cells using reverse transcriptase-polymerase chain reaction (RT-PCR), zymography and immunoblotting. Corneal ulcers with typical ring abscesses were observed 12-24 h after infection, and MMPs, particularly MMP-9, were upregulated in infected corneas. Pseudomonal elastase caused the most extensive damage to both cell types. RCF treated with pseudomonal exoproteases or LPS expressed and secreted MMP-9. Exotoxin A had no effect on MMP expression. Both IL-1beta and TNF-alpha augmented MMP-9 expression in HT1080 cells. Pseudomonal elastase proteolytically activated MMP-2 and MMP-9 released from the cells. In conclusion, corneal destruction seen with P. aeruginosa infections may result from enhanced expression of MMPs by corneal stromal cells stimulated with pseudomonal exoproteases and proinflammatory cytokines and the proteolytic activation of MMPs by pseudomonal elastase.
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PMID:Matrix metalloproteinases induction by pseudomonal virulence factors and inflammatory cytokines in vitro. 1174 75

Pseudomonas aeruginosa keratitis destroys the cornea in susceptible (B6), but not resistant (BALB/c) mice. To determine mechanisms mediating resistance, the role of IFN-gamma, IL-12, and IL-18 was tested in BALB/c mice. RT-PCR analysis detected IFN-gamma mRNA expression levels in cornea that were significantly increased at 1-7 days postinfection. IL-18 mRNA was detected constitutively in cornea and, at 1-7 days postinfection, levels were elevated significantly, while no IL-12 mRNA was similarly detected. To test whether IL-18 contributed to IFN-gamma production, mice were treated with anti-IL-18 mAb. Treatment decreased corneal IFN-gamma mRNA levels, and bacterial load and disease increased/worsened, compared with IgG-treated mice. To stringently examine the role of IFN-gamma in bacterial killing, knockout (-/-) vs wild-type (wt) mice also were tested. All corneas perforated, and bacterial load was increased significantly in -/- vs wt mice. Because disease severity was increased in IFN-gamma(-/-) vs IL-18-neutralized mice, and since IL-18 also induces production of TNF, we tested for TNF-alpha in both groups. ELISA analysis demonstrated significantly elevated corneal TNF-alpha protein levels in IFN-gamma(-/-) vs wt mice after infection. In contrast, RT-PCR analysis of IL-18-neutralized vs IgG-treated infected mice revealed decreased corneal TNF-alpha mRNA expression. Next, to resolve whether TNF was required for bacterial killing, TNF-alpha was neutralized in BALB/c mice. No difference in corneal bacterial load was detected in neutralized vs IgG-treated mice. These data provide evidence that IL-18 contributes to the resistance response by induction of IFN-gamma and that IFN-gamma is required for bacterial killing.
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PMID:IL-18 contributes to host resistance against infection with Pseudomonas aeruginosa through induction of IFN-gamma production. 1202 76

Herpetic stromal keratitis (HSK) is an immunopathologic disease triggered by infection of the cornea with HSV. Key events in HSK involve the interaction between cornea-infiltrating inflammatory cells and resident cells. This interaction, in which macrophages, producing IL-1 and TNF-alpha, and IFN-gamma-producing Th1 cells play a crucial role, results in the local secretion of immune-modulatory factors and a major influx of neutrophils causing corneal lesions and blindness. The Th1-derived cytokine IL-17 has been shown to play an important role in several inflammatory diseases characterized by a massive infiltration of neutrophils into inflamed tissue. Here we show that IL-17 is expressed in corneas from patients with HSK and that the IL-17R is constitutively expressed by human corneal fibroblasts (HCF). IL-17 exhibited a strong synergistic effect with TNF-alpha on the induction of IL-6 and IL-8 secretion by cultured HCF. Secreted IL-8 in these cultures had a strong chemotactic effect on neutrophils. IL-17 also enhanced TNF-alpha- and IFN-gamma-induced secretion of macrophage-inflammatory proteins 1alpha and 3alpha, while inhibiting the induced secretion of RANTES. Furthermore, considerable levels of IFN-gamma-inducible protein 10 and matrix metalloproteinase 1 were measured in stimulated HCF cultures, while the constitutive secretion of monocyte chemotactic protein 1 remained unaffected. The data presented suggest that IL-17 may play an important role in the induction and/or perpetuation of the immunopathologic processes in human HSK by modulating the secretion of proinflammatory and neutrophil chemotactic factors by corneal resident fibroblasts.
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PMID:IL-17 expression in human herpetic stromal keratitis: modulatory effects on chemokine production by corneal fibroblasts. 1242 73

Emerging evidence indicates that intracellular signaling cascades mediate entry of pathogenic adenoviruses into target host cells as well as some of the undesirable inflammatory responses to adenoviral gene vectors. We found that Ad19 infection of cultured human corneal fibroblasts induced IL-8 gene transcription independently of IL-1beta, TNF-alpha, and viral gene expression, suggesting that intracellular signaling events might mediate early inflammatory events in adenovirus keratitis. Heat but not UV light inactivation of the virus abrogated the effect of infection on IL-8 mRNA and protein levels, consistent with a viral binding-mediated mechanism. The tyrosine kinase inhibitor herbimycin blocked Ad19-induced IL-8 expression. Western blot analysis revealed tyrosine phosphorylation of the functionally related kinases c-Src and extracellular signal-regulated kinase (ERK) 1/2 in corneal fibroblasts within 15 min after infection. Respective inhibitors of these kinases, PP2 and PD98059, also blocked Ad19-induced IL-8 mRNA and protein expression. Application of inhibitors to Src and ERK kinase assays suggested an upstream relationship of c-Src to ERK. Finally, DNA microarray studies performed 1 h after Ad19 or mock infection of corneal fibroblasts in the presence or absence of the Src-specific inhibitor PP2 confirmed a relationship between c-Src and IL-8 expression in Ad19-infected corneal cells. c-Src may act as a global regulator of early proinflammatory host responses to Ad19 infection of the human cornea.
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PMID:Corneal IL-8 expression following adenovirus infection is mediated by c-Src activation in human corneal fibroblasts. 1279 55

The role of immunologic factors in the development of ophthalmic pathologies in persons infected by hepatitis B virus (HBV) affecting the liver or in asymptomatic virus carriers (a total of 285 persons, 328 eyes) was studied. The deficit of CD3 and CD4 cells, gammopathy, increased levels of circulating immune complexes and of TNF-alpha in the serum; the deficit of IgA and an enhanced secretion of IgG in the lachrymal fluid; as well as a weakened ability of the local and systematic production of IFN-alpha were typical for a majority of patients. The most profound changes were detected in cases of uveitis; apart from the above mentioned, an increase of the CD4/CD8 index as well as of organ-specific and inter-organ immunization was found. The cases of keratitis (92% of the stromal type) were distinguished through a hypersecretion of TNF-alpha both in the serum and in the lachrymal fluid. Complicated cataracts were observed mainly in convalescents or in asymptomatic virus carriers; immune disorders were less seldom encountered in this category, as compared to the cases of eye inflammations, and basically they were local. The obtained data were considered in treatment. Imunofan, when added to the traditional therapy (symptomatic and corticosteroid one), activated the local and systematic antiviral immunity, suppressed the production of pro-viral cytokines and reduced the autoimmune reactions. As a result of this, the treatment time, the frequency rate of relapses as well as the number of anti-inflammatory and postoperative (in cataracts) complications decreased. The study results are indicative of that the immunopathological reactions, which are typical of HBV patients, can be detected at the ocular level and they can provoke ophthalmic pathologies. The nature, severity and relation between the local and systematic immune disorders predetermine, to a considerable extent, the development of an eye disease and its severity. The treatment (and prophylaxis) of HBV-associated ophthalmic pathologies require an obligatory usage of immunity-correcting means and clinical-and-immunological monitoring.
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PMID:[The role of immunopathological reactions in the development of eye diseases in persons infected by hepatitis B virus and the efficiency of immuno-correcting therapy]. 1280 Apr 83


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