High-dose hydrocortisone reduces expression of the pro-inflammatory chemokines CXCL8 and CXCL10 in SARS coronavirus-infected intestinal cells.
Clinical observations and our high-density oligonucleotide microarray results demonstrated increased expression of proinflammatory chemokines after SARS-CoV infection. Here, we investigated the influence of SARS-CoV infection on CXCL8 (interleukin 8) and CXCL10 (interferon-gamma-inducible protein 10) in human intestinal epithelial (Caco2) cells. RT-PCR and ELISA showed time-dependent up-regulation of both chemokines after SARS-CoV infection. Electric mobility shift assay revealed increased DNA binding activity of the cellular transcription factors activator protein 1 (AP-1) and nuclear factor (B (NF-kappaB) in SARS-CoV infected cells. High hydrocortisone concentrations (> or =50 microg/ml) completely prevented increased DNA binding activity of AP-1 and NF-kappaB and inhibited up-regulation of CXCL8 and CXCL10, but did not reduce chemokine expression to basal levels. Ribavirin that does not inhibit SARS-CoV replication in Vero cells inhibited SARS-CoV replication in Caco2 cells at therapeutical concentrations. Hydrocortisone neither influenced SARS-CoV titres alone nor in combination with ribavirin. Our results show that corticosteroids may be of limited benefit in the suppression of chemokine production by SARS-CoV-infected cells.
Cinatl
Jindrich
J
Institute for Medical Virology, University Hospital Medical School, D-60596 Frankfurt am Main, Germany. cinatl@em.uni-frankfurt.de
Michaelis
Martin
M
Morgenstern
Birgit
B
Doerr
Hans Wilhelm
HW
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC / Q000096:biosynthesis*; D002522:Chlorocebus aethiops; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000821:virology*; D004247:DNA / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic; D006854:Hydrocortisone / Q000494:pharmacology*; D007249:Inflammation; D016209:Interleukin-8 / Q000096:biosynthesis*; D007422:Intestines / Q000166:cytology*; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012254:Ribavirin / Q000494:pharmacology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000378:metabolism*; D045169:Severe Acute Respiratory Syndrome / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation; D014709:Vero Cells
D000893:Anti-Inflammatory Agents; D000963:Antimetabolites; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; D018925:Chemokines; D019743:Chemokines, CXC; D016209:Interleukin-8; D012254:Ribavirin; D004247:DNA; D006854:Hydrocortisone