Activation of p38 MAPK by feline infectious peritonitis virus regulates pro-inflammatory cytokine production in primary blood-derived feline mononuclear cells.
Feline infectious peritonitis (FIP) is an invariably fatal disease of cats caused by systemic infection with a feline coronavirus (FCoV) termed feline infectious peritonitis virus (FIPV). The lethal pathology associated with FIP (granulomatous inflammation and T-cell lymphopenia) is thought to be mediated by aberrant modulation of the immune system due to infection of cells such as monocytes and macrophages. Overproduction of pro-inflammatory cytokines occurs in cats with FIP, and has been suggested to play a significant role in the disease process. However, the mechanism underlying this process remains unknown. Here we show that infection of primary blood-derived feline mononuclear cells by FIPV WSU 79-1146 and FIPV-DF2 leads to rapid activation of the p38 MAPK pathway and that this activation regulates production of the pro-inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta). FIPV-induced p38 MAPK activation and pro-inflammatory cytokine production was inhibited by the pyridinyl imidazole inhibitors SB 203580 and SC 409 in a dose-dependent manner. FIPV-induced p38 MAPK activation was observed in primary feline blood-derived mononuclear cells individually purified from multiple SPF cats, as was the inhibition of TNF-alpha production by pyridinyl imidazole inhibitors.
Regan
Andrew D
AD
Department of Microbiology and Immunology, C4127 Veterinary Medical Center, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
Cohen
Rebecca D
RD
Whittaker
Gary R
GR
D000818:Animals; D002415:Cats; D002467:Cell Nucleus / Q000201:enzymology; D016207:Cytokines / Q000096:biosynthesis*; D004789:Enzyme Activation; D016766:Feline Infectious Peritonitis / Q000821:virology*; D028301:Feline Panleukopenia Virus / Q000472:pathogenicity* / Q000502:physiology; D007249:Inflammation / Q000821:virology; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000821:virology; D014779:Virus Replication; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D016207:Cytokines; D048051:p38 Mitogen-Activated Protein Kinases