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

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Histamine augments collagen content via H1 receptor stimulation in cultures of myofibroblasts taken from wound granulation tissue Monika Wolak1 · Ewa Bojanowska1 · Teresa Staszewska1 · Lucyna Piera2 · Jacek Szymański3 · Jacek Drobnik2  Received: 22 April 2020 / Accepted: 6 November 2020 © The Author(s) 2020

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. Keywords  Collagen · Cell culture · Histamine · Myofibroblast · Fibrosis · Healing

Introduction Wound repair is a complex phenomenon comprising several interdependent processes such as hemostasis, inflammation, cell migration and proliferation, and protein synthesis, as well as wound contraction and remodeling. A fundamental element of the wound environment is constituted by the cells that participate in all repair processes, e.g., fibroblasts, myofibroblasts, epithelial cells, endothelial cells, and * Jacek Drobnik [email protected] 1



Department of Behavioral Pathophysiology, Chair of General and Experimental Pathology, Medical University of Lodz, ul. Żeligowskiego 7/9, Lodz, Poland

2



Laboratory of Connective Tissue Metabolism, Department of Pathophysiology, Chair of General and Experimental Pathology Medical University of Lodz, ul. Żeligowskiego 7/9, Lodz, Poland

3

Central Scientific Laboratory, Medical University of Lodz, Lodz, Poland



leukocytes. The cells are sources and targets of the signals derived from the wound milieu or the regulatory systems of the organism. The signal can be potentialized or inhibited in the wound environment; however, it then must be translated into intracellular information which can influence the metabolism o