HCMV IL-10 suppresses cytokine expression in monocytes through inhibition of nuclear factor-kappaB.
Modulation of host immune responses is a common strategy for promoting virus persistence and avoiding clearance. Human cytomegalovirus (HCMV) is known to encode numerous immunomodulatory genes, including a homolog of the cytokine human interleukin-10 (hIL-10). While having limited sequence homology to hIL-10, cytomegalovirus IL-10 (cmvIL-10) shares many functional characteristics with the human cytokine and acts as a potent suppressor of the inflammatory immune response. The mechanism by which hIL-10 inhibits inflammatory cytokines involves a transcriptional block via inhibition of nuclear factor-kappaB (NF-kappaB) activity. To determine whether cmvIL-10 employs the same mechanism to inhibit cytokine production, the effect of cmvIL-10 on NF-kappaB signaling in monocytes was investigated. The results demonstrate that cmvIL-10 does inhibit NF-kappaB activation, as evidenced by reduced degradation of the NF-kappaB inhibitor IkappaB-alpha, and decreased transcription of the NF-kappaB-responsive genes tumor necrosis factor-alpha (TNF-alpha) and IL-1beta. These studies confirm that cmvIL-10 mediates cytokine suppression by blocking NF-kappaB transcriptional activity in human monocytes.
Nachtwey
James
J
Department of Biology, University of San Francisco, San Francisco, California 94117, USA.
Spencer
Juliet V
JV
D002460:Cell Line; D016207:Cytokines / Q000235:genetics* / Q000276:immunology; D003587:Cytomegalovirus / Q000235:genetics / Q000276:immunology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D015536:Down-Regulation; D015870:Gene Expression; D006801:Humans; D020672:I-kappa B Proteins / Q000235:genetics / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000821:virology; D016328:NF-kappa B / Q000235:genetics* / Q000276:immunology; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
D016207:Cytokines; D020672:I-kappa B Proteins; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins; D016753:Interleukin-10