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)

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.
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PMID:Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. 903 56

Purpose. To investigate the expression and function of toll-like receptors (TLRs) during experimental keratomycosis. Methods. Scarified corneas of BALB/c mice were topically inoculated with Candida albicans and compared with control corneas by a murine gene microarray and immunostaining. Real-time reverse transcription polymerase chain reaction (RT-PCR) determined relative TLR gene expression in murine and human donor corneas. The scarified corneas of TLR2(-/-) mice, TLR4(-/-) mice, and C57BL/6J control mice were also inoculated with C. albicans, to determine relative severity, fungal load, and cytokine transcript levels. Results. TLR1, -2, -4, -6, and -13 were significantly upregulated (5- to 10-fold; P < 0.01) by microarray, and TLR1, -2, -4, and -13 were significantly increased (4- to 11-fold; P < 0.05) by real-time RT-PCR in BALB/c murine corneas. Similarly, TLR2, -6, and -13 were significantly upregulated (5- to 16-fold; P < or = 0.001) by real-time RT-PCR in C57BL/6J murine corneas the day after inoculation, and TLR2 and -13 remained significantly (P < 0.05) increased after 1 week. TLR2 transcript was also upregulated twofold (P = 0.04) in C. albicans-inoculated explanted human corneas. Although murine keratitis severity scores were similar, significantly more fungi were recovered from TLR2(-/-) mouse corneas (P = 0.04) than from TLR4(-/-) mouse corneas (P = 0.9). Tumor necrosis factor-alpha, interleukin 23, chemokine C-C ligands 3 and 4, and dectin-1 were significantly (P < 0.05) downregulated in C. albicans-infected corneas of TLR2(-/-) mice. Conclusions. TLR2 signals proinflammatory cytokines that control fungal growth during C. albicans keratitis. TLR13 may have an additional role in the innate immune response of murine corneal candidiasis.
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PMID:Toll-like receptors involved in the pathogenesis of experimental Candida albicans keratitis. 1993 94

Fungal keratitis is a corneal disease with a high blindness rate caused by pathogenic fungal infections. The pathogenesis of fungal keratitis and the immune response after fungal infection are still unclear. Notably, the pathological features of fungal keratitis in tree shrews are similar to those in humans. In the present study, mRNA profiling of tree shrew corneas with fungal keratitis was performed. GO and KEGG enrichment analyses were performed on the differentially expressed mRNAs, and the GO biological process ontology was used to analyze functional trends in the differentially expressed mRNAs. In total, 151 downregulated and 71 upregulated mRNAs were shared among the 7-day, 14-day and 30-day infection groups. These differentially expressed mRNAs were significantly enriched in the GO category immune response (GO: 0002376) and the KEGG pathways cytokine receptor binding (KEGG ID: tup04060) and cell adhesion (KEGG ID: tup04514). The downregulated mRNAs were significantly enriched in the corneal epithelial cell adhesion function. Fifty-eight initially upregulated mRNAs gradually decreased in expression, and these mRNAs were significantly enriched in the functions lipopolysaccharide (LPS) and antibacterial polypeptide recognition, cell differentiation, and cell rearrangement. Zeta chain of T-cell receptor associated protein kinase 70 (ZAP70), lymphocyte cytosolic protein 2 (LCP2), C-C motif chemokine and its receptor showed high degrees of connectivity in the protein-protein interaction (PPI) network. We speculate that the decrease in symptoms of tree shrew fungal keratitis may be related to the upregulation of genes involved in immune regulation and macrophage colony stimulation. This study showed that the C-C motif chemokine and its receptor may play a key role in regulating tree shrew fungal keratitis, providing a theoretical basis for studying the pathogenesis of human fungal keratitis.
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PMID:mRNA profiling reveals response regulators of decreased fungal keratitis symptoms in a tree shrew model. 3205 30