The role of histamine in the regulation of the viability, proliferation and transforming growth factor ß1 secretion of rat wound fibroblasts

Background: Inflammation mediators play a regulatory role in repair processes. The study will examine the influence of histamine on wound fibroblast metabolic activity, viability, proliferation, and TGFß1 secretion. The study also will identify the histamine receptor involved in regulation of the tested repair processes. Methods: Fibroblasts were obtained from the granulation tissue of wounds or intact dermis of rats. The MTT and BrdU assays were used to examine the effect of histamine (10^-8M-10^-4M) on the viability and metabolic activity of fibroblasts, and on their proliferative capacity. The influence of histamine receptor antagonists (i.e., ketotifen, ranitidine, ciproxifan and JNJ7777120) and agonists (2-pyridylethlamine dihydrochloride, amthamine dihydrobromide) was also investigated. The TGFß1 and histamine receptors H1 were evaluated by enzyme-linked immunosorbent assay. Results: Histamine significantly increased granulation tissue fibroblast viability and metabolic activity at 10^-8and 10^-6M but did not change their proliferative activity. Only the blockade of the H1 receptor removed this effect of histamine. H1 receptor agonist (2-pyridylethlamine dihydrochloride) increased cell viability, thereby mimicking histamine action. Both Histamine (10^-4M) and 2-pyridylethlamine dihydrochloride increased TGFß1 concentration in cell culture medium. However, ketotifen blocked histamine-induced augmentation of TGFß1. H1 receptor expression on wound fibroblasts was confirmed. Conclusion: The regulatory influence of histamine on wound fibroblast function (viability/metabolic activity or secretion of TGFß1) is dependent on H1 receptor stimulation. Contrary to wound fibroblasts, these cells express a very low level of H1 receptors when isolated from intact dermis and histamine is unable to modify their metabolic activity.