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

Herpes simplex virus type 1 (HSV-1) infection on the murine cornea induces an intense inflammatory response which can lead to blindness. This disease, known as herpes stromal keratitis, can be prevented by the timely passive transfer of monoclonal antibody specific for viral glycoprotein D (gD). Precisely how antibody treatment prevents excessive corneal inflammation is not known. In this study we investigated whether chemokine mRNA expression is inhibited by antibody treatment. Total cellular RNAs isolated from normal corneas and at various times after virus infection were analyzed via reverse transcription-PCR for mRNA coding for seven different chemokines. Constitutive levels of IP-10, KC, MIP-2, MCP-1, MIP-1 beta, and RANTES mRNA were detected in uninfected corneas of BALB/c mice. When the cornea was mechanically traumatized, message for all six chemokines was transiently elevated above constitutive levels. In contrast, HSV-1 infection resulted in prolonged enhanced chemokine message expression. The kinetics of mRNA accumulation was distinctive for each chemokine analyzed. MIP-1 alpha message, not detected constitutively, was not evident until day 7 postinfection. Administration of anti-HSV gD monoclonal antibody 1 day after infection was associated with reduced message for MIP-2, MCP-1, MIP-1 alpha, and MIP-1 beta. IP-10, KC, and RANTES messages were not altered. Collectively, our results suggest that anti-gD treatment may protect, at least in part, by inhibiting production of chemokines believed to promote inflammation.
 ...
PMID:Protective antibody therapy is associated with reduced chemokine transcripts in herpes simplex virus type 1 corneal infection. 855 95

Corneal inflammation (keratitis) is a major cause of visual impairment in Onchocerca volvulus infection. Previous studies showed that onchocercal keratitis can be induced in mice following s.c. immunization and intracorneal injection with soluble O. volvulus Ags (OvAg), and that the inflammatory response is dependent on T cells and IL-4. Since recombinant IL-12 impairs IL-4-dependent, Th2-mediated responses in other parasitic infections and in models of allergic asthma, the present study was undertaken to determine the effect of IL-12 on onchocercal keratitis. Mice were injected i.p. with IL-12 or saline at the time of initial sensitization to OvAg. Surprisingly, IL-12 treatment caused significant exacerbation of corneal pathology, which was associated with increased eosinophil and mononuclear cell infiltration into the corneal stroma. Consistent with the well-documented effect of IL-12 on Th1 cell development, corneas of IL-12-treated animals had elevated expression of the Th1 cytokine IFN-gamma and diminished expression of the Th2 cytokines IL-4, IL-5, IL-10, and IL-13. However, corneas from these animals also had marked elevation of alpha- and beta-chemokines known to be active on eosinophils and mononuclear cells, including IFN-gamma-inducible protein (IP)-10, macrophage inflammatory protein-1alpha, macrophage inflammatory protein-1beta, JE/monocyte chemotactic protein-1, RANTES (regulated upon activation, normal T expressed and secreted), and eotaxin. Together, these data indicate that IL-12 exacerbates OvAg-mediated corneal pathology by enhancing chemokine expression and recruitment of inflammatory cells.
 ...
PMID:IL-12 exacerbates helminth-mediated corneal pathology by augmenting inflammatory cell recruitment and chemokine expression. 899

The chemokines are a large group of chemotactic cytokines that regulate leukocyte trafficking and have recently been shown to inhibit human immunodeficiency virus entry into cells. Eotaxin is a C-C chemokine implicated in the recruitment of eosinophils in a variety of inflammatory disorders and, unlike all other eosinophil chemoattractants, is eosinophil specific. However, given the large number of chemoattractants that have activities on eosinophils, it is unclear whether eotaxin has an important role in vivo. Furthermore, it remains unclear why there is constitutive expression of eotaxin in healthy states in the absence of eosinophilic inflammation. To begin to determine the significance of eotaxin at baseline and during eosinophil-mediated disease processes, we have used targeted gene disruption to generate mice that are deficient in eotaxin. Such mice demonstrate that eotaxin enhances the magnitude of the early (but not late) eosinophil recruitment after antigen challenge in models of asthma and stromal keratitis. Surprisingly, a role for eotaxin in regulating the constitutive number of eosinophils in the peripheral circulation is also demonstrated. These results indicate a contributory role for eotaxin in the generation of peripheral blood and antigen-induced tissue eosinophilia.
 ...
PMID:Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. 903 56

Herpes simplex virus type 1 (HSV-1) infection of the murine cornea results in a tissue-destructive inflammatory response. In this study we show that virus infection induces the synthesis of macrophage inflammatory protein-2 (MIP-2), MIP-1alpha, and monocyte chemoattractant protein-1 (MCP-1). However, only the production of MIP-2 and MIP-1alpha coincided with the influx of leukocytes into the cornea. IL-10 treatment markedly suppressed chemokine message and protein synthesis in vivo. Local administration of IL-10 also dramatically reduced the number of T cells and neutrophils migrating into the cornea and suppressed the severity of corneal disease. The inflammatory response could also be suppressed by the passive transfer of neutralizing antibody to MIP-1alpha but not MCP-1. We conclude that local IL-10 administration can suppress chemokine synthesis, thereby ameliorating corneal disease. Furthermore, our results indicate that MIP-1alpha plays a major role in herpes stromal keratitis development, whereas MCP-1 does not.
 ...
PMID:Chemokine synthesis in the HSV-1-infected cornea and its suppression by interleukin-10. 954 79

The role played by chemokines in disease process is an active area of research that continues to uncover new players. In this report we discuss the likely role of selected chemokines in the disease herpetic stromal keratitis (HSK). This lesion occurs as a sequel to herpes simplex virus infection and is currently accepted as an immunopathological process which primarily involves CD4+ T lymphocytes. In this review we discuss the events involved in HSK, the chemokine profile associated with this disease, and speculate on cellular activities and molecular events which characterize HSK as an immunopathological disease.
 ...
PMID:Chemokines and ocular pathology caused by corneal infection with herpes simplex virus. 1019 Jun 89

Pseudomonas aeruginosa can cause ulcerative bacterial keratitis. A feature of keratitis is the rapid infiltration of the avascular corneal stroma by neutrophils. KC is a potent neutrophil chemokine. The present study used a mouse model of ocular infection to assess the relationship between KC and inflammation in the cornea in response to challenge with a strain of P. aeruginosa causing keratitis. Low levels of KC mRNA and protein were detected by in situ hybridization and ELISA, respectively, in unchallenged corneas. Dramatically increased numbers of KC mRNA+ cells were present in P. aeruginosa strain 6294-challenged corneas. Expression of KC mRNA was found to be up-regulated in the corneal epithelium in response to wounding alone. The KC mRNA+ cells were located in the epithelium and corresponding to infiltrating neutrophils cells in the stroma. Quantification of KC protein at different time points showed peak levels at 8 h of bacterial challenge. These results suggest that KC may be involved with the regulation of leucocyte infiltration early during bacterial keratitis.
 ...
PMID:KC production in the cornea in response to Pseudomonas aeruginosa challenge. 1065 22

Herpetic stromal keratitis (HSK) is an inflammatory disease of the cornea that often results in blindness. It is mediated by a host immune response which is triggered by herpes simplex virus (HSV) infection. Immune effector mechanisms are hypothesized to be important in disease development. We investigated, in a mouse model, whether perforin-dependent cytotoxicity is an important effector mechanism in the production of HSK. Wild-type (C57BL/6) and perforin-deficient (PKO) mice were infected intracorneally with HSV-1 strain F. Clinical disease and histologic lesions of the cornea at 23 days postinfection (p.i.) were significantly less severe in HSV-1-infected PKO mice than in infected wild-type mice. mRNA for the chemokine macrophage inflammatory protein 1alpha (MIP-1alpha) was detected by reverse transcription-PCR in the corneas of infected wild-type mice but not in the corneas of infected PKO mice at 23 days p.i. Adoptive transfer of wild-type HSV-1 immune T-cell-enriched splenocytes into HSV-1-infected PKO mice restored the disease phenotype which was seen in infected wild-type mice. In contrast, mice carrying a null-function mutation in the Fas ligand, which is involved in an alternative cytotoxic mechanism, developed clinical disease and histologic lesions which were comparable to those in wild-type mice. Viral clearance from the eyes of PKO mice was not impaired. There was no significant difference between the infectious viral titers isolated from the eyes of PKO and wild-type mice. Our findings show that perforin is important in the pathogenesis of HSK.
 ...
PMID:Pathogenesis of herpes simplex virus type 1-induced corneal inflammation in perforin-deficient mice. 1109 Jan 83

Topical application of plasmid DNA encoding IL-12 to the cornea of mice prior to ocular infection with Herpes simplex virus type 1 (HSV) results in diminished corneal immunoinflammatory lesions. Such herpetic stromal keratitis (HSK) reactions in humans represent an important cause of blindness. The effect of IL-12 pretreatment acted via inhibitory effects on corneal neovascularization rather than by inhibiting viral replication or the function of CD4(+) T cells that mediate HSK. The antiangiogenesis induced by IL-12 DNA application was mediated indirectly via the cytokine IFN-gamma and one or both of two chemokine molecules, IP-10 and MIG. Thus IL-12 DNA administration lacked modulatory effects on HSK in GKO mice, indicating the necessary involvement of IFN-gamma induction for antiangiogenesis. In contrast, exposure of GKO mice to IP-10 DNA did suppress the severity of HSK. Furthermore, treatment with specific antisera to IP-10 and MIG in HSV-infected mice abrogated the IL-12-induced inhibitory effect on lesion severity. Taken together, our data indicate that the HSV-induced ocular immunoinflammatory lesions can be modulated by IL-12 and that this effect results from chemokine inhibition of angiogenesis. The use of antiangiogenesis therapy might represent a useful control measure against HSK.
 ...
PMID:IL-12 suppresses the expression of ocular immunoinflammatory lesions by effects on angiogenesis. 1186 84

The aim of this study was to elucidate the expression of chemokines, their role and regulation in bacterial corneal infection using three bacterial strains (Pseudomonas. aeruginosa- invasive, cytotoxic and contact lens induced acute red eye strains) which have been shown to produce three distinct patterns of corneal disease in the mouse. The predominant chemokine expressed in response to all three strains was MIP-2. Prolonged expression of high levels of MIP-2 was associated with increased severity of corneal inflammation. Significantly reduced disease severity upon administration of anti-MIP-2 antibodies suggested that MIP-2 may play an important role in the pathogenesis of Pseudomonas keratitis at least in part by being a major chemoattractant for polymorphonuclear leukocytes (PMN) recruitment. Interestingly, the numbers of bacteria in eyes with neutralized MIP-2 activity did not decrease even though the severity of the disease was decreased. This implies PMNs as the major destructive factor in microbial keratitis. Further, neutralization of IL-1beta activity alone using monoclonal antibodies resulted in significant reduction of both MIP-2 and KC activity indicating that chemokine levels were regulated by IL-1beta. These studies demonstrate that the regulation of MIP-2 activity may be beneficial in reducing corneal damage during microbial keratitis in rodents and perhaps that regulation of the human homologue of MIP-2, IL-8, may be useful for controlling keratitis in humans.
 ...
PMID:Role and regulation of CXC-chemokines in acute experimental keratitis. 1256 10

Herpetic stromal keratitis (HSK) is a chronic inflammatory process in corneal stroma that results from recurrent HSV type 1 infection. We used the murine model of HSK to demonstrate the importance of the interaction between an inducible T cell costimulatory receptor, 4-1BB, and its ligand, 4-1BB ligand (4-1BBL), in the development of this disease. In BALB/c mice, HSK ordinarily induced by infection with the RE strain of herpes was prevented by blocking 4-1BB/4-1BBL interaction, either by deleting 4-1BB (in mutant 4-1BB(-/-) mice) or by introducing mAbs against 4-1BBL. The majority of T cells infiltrating the infected corneas were 4-1BB(+) activated effector cells that expressed cell surface markers CD44, CD25, and/or CD62L, as well as chemokine receptors CCR1, CCR2, and CCR5, and a limited number of TCR Vbeta chains (Vbeta8.1/8.2, Vbeta8.3, Vbeta10b, and Vbeta5.1/5.2, in order of abundance). Analysis of cell surface phenotypes showed that the failure to develop HSK in the 4-1BB(-/-) mice was associated with a reduced expression of CD62L at the time of T cell migration into the corneal stroma.
 ...
PMID:Blocking 4-1BB/4-1BB ligand interactions prevents herpetic stromal keratitis. 1284 21


1 2 3 4 Next >>