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

Human cytomegalovirus (HCMV) infection is associated with excessive proinflammatory immune responses such as cytokine/chemokine production or upregulation of adhesion molecules on the host cells. It is assumed that these features of HCMV-related immunopathology can not be treated effectively with currently available anti HCMV drugs. In the present study the efficacy of ganciclovir (GCV), foscarnet (PFA), cidofovir (HPMPC), and ISIS 2922, an antisense oligonucleotide complementary to HCMV immediate-early (IE) mRNA, was investigated on HCMV-induced secretion and functional activity of the C-X-C chemokine IL-8 and the expression of the intercellular adhesion molecule-1 (ICAM-1). As compared with mock-infected cells IL-8 production was increased up to 9-fold and ICAM-1 expression up to 4-fold in HCMV-infected fibroblasts. Treatment of infected cells with GCV (40 microM), PFA (200 microM) or HPMPC (2 microM) suppressed completely virus replication as demonstrated by quantification of late (L) antigen expression and infectious virus production. These drugs, however, failed to inhibit IE antigen expression and did not prevent HCMV-induced upregulation of IL-8 and ICAM-1. In contrast, ISIS 2922 (1 microM) suppressed both IE and L antigen expression by 99% and inhibited infectious virus production by 10(4)-fold. Moreover, ISIS 2922 significantly suppressed HCMV-induced upregulation of both IL-8 and ICAM-1 expression on the transcriptional and on the protein level. Our results indicate that ISIS 2922 but not inhibitors of HCMV DNA prevents HCMV-induced upregulation of IL-8 and ICAM-1, both hallmarks of inflammatory processes. Thus, inhibition of HCMV IE expression with ISIS 2922 may be an important strategy for the treatment of HCMV-related immunopathogenesis.
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PMID:The antisense oligonucleotide ISIS 2922 prevents cytomegalovirus-induced upregulation of IL-8 and ICAM-1 in cultured human fibroblasts. 1063 Sep 64

Canine cells of different histogenesis were infected with the Onderstepoort strain of distemper virus (CDV) to study the effect of viral infection on cytokine production. Included were primary brain cells, dermal fibroblasts, and two cell lines, DH 82 cells (macrophage-like) and epithelial Madin-Darby canine kidney (MDCK) cells. All cultures produced infective virus. MDCK cells had the lowest percentage of CDV-antigen positive cells, and infection did not cause a significant increase of cell death. After infection, mRNA steady state levels of interleukin (IL)-1, IL-6, IL-8, IL-12, tumor necrosis factor-alpha (TNF), and transforming growth factor-beta (TGF) were analyzed using RT-PCR. IL-6 and TNF protein were assessed immunohistochemically. In general, CDV infection resulted in induction of pro-inflammatory cytokines. In primary brain and DH 82 cells, IL-1, IL-6, and TNF were induced, and IL-1 and TNF but not IL-6 were upregulated in dermal fibroblasts. In contrast, in MDCK cells IL-1 and TNF expression was similar in infected and noninfected cells, whereas IL-6 was not produced in either condition. In addition, cytokine induction correlated to the degree of level of CDV production, and therefore cytopathic effects are presumed to be due to a direct virus-mediated or cytokine-mediated process. These findings suggest that pro-inflammatory cytokines, namely IL-1, IL-6, and TNF, which might play an important role in CDV pathogenesis, are induced in a cell-specific manner.
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PMID:Cell type-dependent cytokine expression after canine distemper virus infection. 1247 98