Related Experiment Video
Updated: Jul 11, 2026

Generation and Culturing of Primary Human Keratinocytes from Adult Skin
Published on: December 22, 2017
Histamine enhances the production of human beta-defensin-2 in human keratinocytes
Naoko Kanda1, Shinichi Watanabe
1Department of Dermatology, Teikyo University School of Medicine, Tokyo, Japan.
Abstract:
The anti-microbial peptide human beta-defensin-2 (hBD-2), produced by epidermal keratinocytes, plays pivotal roles in anti-microbial defense, inflammatory dermatoses, and wound repair. hBD-2 induces histamine release from mast cells. We examined the in vitro effects of histamine on hBD-2 production in normal human keratinocytes. Histamine enhanced TNF-alpha- or IFN-gamma-induced hBD-2 secretion and mRNA expression. Histamine alone enhanced transcriptional activities of NF-kappaB and activator protein-1 (AP-1) and potentiated TNF-alpha-induced NF-kappaB and AP-1 activities or IFN-gamma-induced NF-kappaB and STAT1 activities. Antisense oligonucleotides against NF-kappaB components p50 and p65, AP-1 components c-Jun and c-Fos, or H1 antagonist pyrilamine suppressed hBD-2 production induced by histamine plus TNF-alpha or IFN-gamma. Antisense oligonucleotide against STAT1 only suppressed hBD-2 production induced by histamine plus IFN-gamma. Histamine induced serine phosphorylation of inhibitory NF-kappaBalpha (IkappaBalpha) alone or together with TNF-alpha or IFN-gamma. Histamine induced c-Fos mRNA expression alone or together with TNF-alpha, whereas it did not further increase c-Jun mRNA levels enhanced by TNF-alpha. Histamine induced serine phosphorylation of STAT1 alone or together with IFN-gamma, whereas it did not further enhance IFN-gamma-induced tyrosine phosphorylation of STAT1. The histamine-induced serine phosphorylation of STAT1 was suppressed by MAPKK (MEK) inhibitor PD98059. These results suggest that histamine stimulates H1 receptor and potentiates TNF-alpha- or IFN-gamma-induced hBD-2 production dependent on NF-kappaB, AP-1, or STAT1 in human keratinocytes. Histamine may potentiate anti-microbial defense, skin inflammation, and wound repair via the induction of hBD-2.
Related Concept Videos
Hypersensitivity Reactions: Delayed Hypersensitivity Reactions
Surface Membrane Barriers
The outer layer of the skin, the epidermis, is a robust barrier comprising layers of closely packed keratinized cells. This dense arrangement prevents microbes from penetrating the body. The periodic shedding of epidermal cells...
Defense Mechanism Against Infection
In addition, many body organ systems have unique defenses against infection. The skin is an intact, multilayered surface preventing invasion by microorganisms unless impaired. Mucous membranes lining the mouth, nose, and eyelids are barriers...
Gastritis II: Pathophysiology
The Skin Microbiota
Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal