Upregulation of IL-6, IL-8 and CCL2 gene expression after acute inflammation: Correlation to clinical pain.
Tissue injury initiates a cascade of inflammatory mediators and hyperalgesic substances including prostaglandins, cytokines and chemokines. Using microarray and qRT-PCR gene expression analyses, the present study evaluated changes in gene expression of a cascade of cytokines following acute inflammation and the correlation between the changes in the gene expression level and pain intensity in the oral surgery model of tissue injury and acute pain. Tissue injury resulted in a significant upregulation in the gene expression of interleukin-6 (IL-6; 63.3-fold), IL-8 (8.1-fold), chemokine (C-C motif) ligand 2 (CCL2; 8.9-fold), chemokine (C-X-C motif) ligand 1 (CXCL1; 30.5-fold), chemokine (C-X-C motif) ligand 2 (CXCL2; 26-fold) and annexin A1 (ANXA1; 12-fold). The upregulation of IL-6 gene expression was significantly correlated to the upregulation of IL-8, CCL2, CXCL1 and CXCL2 gene expression. Interestingly, the tissue injury-induced upregulation of IL-6, IL-8 and CCL2 gene expression, was positively correlated to pain intensity at 3h post-surgery, the onset of acute inflammatory pain. However, ketorolac treatment did not have a significant effect on the gene expression of IL-6, IL-8, CCL2, CXCL2 and ANXA1 at the same time point of acute inflammation. These results demonstrate that the upregulation of IL-6, IL-8 and CCL2 gene expression contributes to the development of acute inflammation and inflammatory pain. The lack of effect of ketorolac on the expression of these gene products may be related to the ceiling analgesic effects of non-steroidal anti-inflammatory drugs.
Wang
Xiao-Min
XM
National Institute of Nursing Research, NIH, Building 10, CRC, Room 2-1339, Bethesda, MD 20892, USA National Institute of Dental and Craniofacial Research, NIH, Bethesda, MD, USA Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
Hamza
May
M
Wu
Tian-Xia
TX
Dionne
Raymond A
RA
D018932:Chemokine CCL2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D005157:Facial Pain / Q000378:metabolism* / Q000517:prevention & control; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000517:prevention & control; D015850:Interleukin-6 / Q000378:metabolism*; D016209:Interleukin-8 / Q000378:metabolism*; D008297:Male; D013223:Statistics as Topic; D015854:Up-Regulation / Q000187:drug effects*; D055815:Young Adult
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D052246:Cyclooxygenase 2 Inhibitors; D015850:Interleukin-6; D016209:Interleukin-8