Diacerein inhibits the pro-atherogenic & pro-inflammatory effects of IL-1 on human keratinocytes & endothelial cells.
We investigated IL-1-induced regulation of genes related to inflammation and atherogenesis in human keratinocytes and endothelial cells, and if 'diacerein', an oral IL-1 inhibiting drug currently approved for use in osteoarthritis, would reverse IL-1's effects on these cells. Primary human keratinocytes and coronary artery endothelial cells were treated with either IL-1α or IL-1β, with and without diacerein. Using PCR-array, we assessed differential gene-expression regulated by IL-1 and diacerein. We identified 34 pro-atherogenic genes in endothelial cells and 68 pro-inflammatory genes in keratinocytes significantly (p<0.05) regulated at least 2-fold by IL-1, in comparison to control. Diacerein completely or partially reversed this regulation on almost all genes. Using ELISA, we confirmed diacerein's ability to reverse IL-1-driven gene-regulation of 11 selected factors, at the protein level. The results support a novel idea that diacerein acts as an inhibitor of the pro-atherogenic and pro-inflammatory effects of IL-1. Diacerein may have therapeutic applications to diminish IL-1-induced skin inflammation in psoriasis and attenuate IL-1-induced development of atherosclerosis. Further investigation into diacerein's effect on skin inflammation, atherogenesis and cardiovascular risk in animal models or humans is warranted.
Department of Dermatology, University of Illinois at Chicago (UIC)-College of Medicine, Chicago, IL, United States of America.
Girish C
GC
Mohan
Department of Dermatology, University of Illinois at Chicago (UIC)-College of Medicine, Chicago, IL, United States of America.
Huayi
H
Zhang
Department of Dermatology, University of Illinois at Chicago (UIC)-College of Medicine, Chicago, IL, United States of America.
Lei
L
Bao
Department of Dermatology, University of Illinois at Chicago (UIC)-College of Medicine, Chicago, IL, United States of America.
Benjamin
B
Many
Department of Dermatology, University of Illinois at Chicago (UIC)-College of Medicine, Chicago, IL, United States of America.|Department of Medicine, Jesse Brown Veterans Affairs Hospital, Chicago, IL, United States of America.|Department of Medicine, Capt. James A. Lovell FHCC, North Chicago, IL, United States of America.
Lawrence S
LS
Chan
D000880:Anthraquinones / Q000494:pharmacology*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000235:genetics; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000473:pathology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000235:genetics; D053582:Interleukin-1alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015603:Keratinocytes / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010003:Osteoarthritis / Q000188:drug therapy*; D011565:Psoriasis / Q000188:drug therapy; D060888:Real-Time Polymerase Chain Reaction
D000880:Anthraquinones; D000893:Anti-Inflammatory Agents; C508584:IL1A protein, human; C508585:IL1B protein, human; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; C025292:diacerein