The role of histamine in the regulation of the viability, proliferation and transforming growth factor β1 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 TGFβ1 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 TGFβ1 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 TGFβ1 concentration in cell culture medium. However, ketotifen blocked histamine-induced augmentation of TGFβ1. H1 receptor expression on wound fibroblasts was confirmed.


CONCLUSIONS
The regulatory influence of histamine on wound fibroblast function (viability/metabolic activity or secretion of TGFβ1) 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.
Department of Behavioral Pathophysiology, Chair of General and Experimental Pathology Medical University of Lodz, Łódź, Poland.
Monika
M
Wolak
Department of Behavioral Pathophysiology, Chair of General and Experimental Pathology Medical University of Lodz, Łódź, Poland.
Ewa
E
Bojanowska
Department of Behavioral Pathophysiology, Chair of General and Experimental Pathology Medical University of Lodz, Łódź, Poland.
Teresa
T
Staszewska
Laboratory of Connective Tissue Metabolism, Department of Neuropeptide Research, Chair of General and Experimental Pathology, Medical University of Lodz, Łódź, Poland.
Joanna
J
Ciosek
Department of Pathophysiology and Experimental Neuroendocrinology, Chair of General and Experimental Pathology, Medical University of Lodz, Łódź, Poland.
Marlena
M
Juszczak
Laboratory of Connective Tissue Metabolism, Department of Neuropeptide Research, Chair of General and Experimental Pathology, Medical University of Lodz, Łódź, Poland. Electronic address: drob@op.pl.
Jacek
J
Drobnik
D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology*; D017442:Histamine Agonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014945:Wound Healing / Q000187:drug effects*
D017442:Histamine Agonists; D006634:Histamine H1 Antagonists; D011969:Receptors, Histamine H1; D053773:Transforming Growth Factor beta1; D006632:Histamine
Fibroblasts; Histamine; MTT; Proliferation; Viability