Histamine augments collagen content via H1 receptor stimulation in cultures of myofibroblasts taken from wound granulation tissue

Abstract

The inflammatory reaction influences the deposition of collagen within wound granulation tissue. The aim of the present study is to determine whether histamine acting directly on myofibroblasts derived from wound granulation tissue may influence collagen deposition. It also identifies the histamine receptor involved in this process. The experiments were carried out on cells isolated from the granulation tissue of a wound model (a polypropylene net inserted subcutaneously to rats) or intact rat skin. Collagen content was measured following the addition of different concentrations of histamine and treatment with histamine receptor antagonists (ketotifen – H1 inhibitor, ranitidine – H2 inhibitor) and a histamine receptor H1 agonist (2-pyridylethylamine dihydrochloride).The cells were identified as myofibroblasts: alpha-smooth muscle actin, vimentin, and desmin positive in all experimental conditions. Histamine increased the collagen level within both cell cultures, i.e., those isolated from granulation tissue or intact skin. It did not, however, influence the expression of either the collagen type I or III genes within the cultured myofibroblasts. Histamine activity was reduced by ketotifen (the H1 receptor inhibitor) and increased by the H1 receptor agonist, as demonstrated by changes in the levels of collagen in the myofibroblast culture. Histamine increased collagen content within the cultures, acting directly on myofibroblasts via H1 receptor stimulation.

Histamine is involved in the regulation of collagen content in cultured heart myofibroblasts via H2, H3 and H4 histamine receptors

“…Hence, it appears that different histamine receptors may be involved in the regulation of collagen content, although the obtained results are dependent on the experimental model, and the selected tissue or species. Previous studies have suggested that different types of histamine receptors participate in the regulation of collagen deposition in various organs or tissues (19,(32)(33)(34). This phenomenon could be dependent on the varying influence of the extracellular environment on myofibroblasts (2).…”

“…Previously, it has been proposed that in the cardiac myofibroblasts obtained from a myocardial infarction scar, the histamine content is mediated by the H 3 receptor (19). However, the effect of histamine was found to be influenced by the H 1 receptor in myofibroblasts from wound granulation tissue (18,32). H 1 receptor activation appears to be involved in the regulation of collagen metabolism within dermal fibroblasts ( 27), whereas blockade of the H 2 receptor decreased collagen type I gene expression in human fibroblasts (28).…”

Chlorpheniramine maleate exerts an anti-keloid activity in vivo and in vitro

“…In rabbit ear hyperplastic scar, long-acting intra-lesioned injection of histamine drug can inhibit the TGF beta l/Smad3 signalling pathway to reduce the collagen synthesis and I/collagen type III proportion, thereby inhibiting scar hyperplasia (41). The regulatory effect of histamine on wound broblast function (activity/metabolic activity or TGFβ1 secretion) is determined by H1 receptor stimulation (42,43). CPM acts as an H1 receptor antagonist with a more substantial antihistamine effect than diphenhydramine and others, and it has been applied clinically as an antihistamine with less dosage and side effects (44,45).…”

Two Sides of the Coin: Mast Cells as a Key Regulator of Allergy and Acute/Chronic Inflammation

“…Histamine, another substance secreted by MCs, also induces fibrosis. It is reported that histamine stimulates fibroblast proliferation and collagen synthesis [ 91 , 92 ]. Histamine has four receptors: H1R, H2R, H3R and H4R.…”