Expression of histidine decarboxylase in melanocytes of the human skin
Introduction
Histamine is a physiologically active amine widely distributed in the peripheral and central nervous systems. It is involved in inflammation, allergic reaction, gastric acid secretion, itching, and neurotransmission in vivo. Furthermore, histamine is stored in the granules of storage-type histamine-producing cells, namely, mast cells and basophils. Schayer and Ganley (1959) and Kahlson et al. (1960) reported the presence of a different type of histamine-producing cell in which the biosynthetic activity of histamine is recognized but the pool for storing itself remains unidentified [1,2]. Histidine decarboxylase (HDC), which is a key enzyme for histamine synthesis, is induced by lipopolysaccharides and cytokines such as interleukin (IL)-1β, tumor necrosis factor-α, granulocyte macrophage-colony stimulating factor, IL-18, and IL-12 [3,4]. Currently, T cells [5,6], B cells [5], macrophages [[7], [8], [9]], neutrophils [10], keratinocytes [11,12], and vascular endothelial cells [13] are regarded as HDC-inducing cells (inducible histamine-producing cells).
Exposure to surfactants or intradermal injection of α-melanocyte–stimulating hormone increases mouse epidermal HDC [14,15], chronic pruritus with unknown cause induces monkey epidermal HDC [16], and atopic dermatitis increases human epidermal HDC [17]. However, HDC-expressing cells have not yet been sufficiently assessed using skin tissue. We report a novel finding obtained from examining the localization of HDC in human healthy skin samples.
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Subjects
Skin of three healthy subjects (age range: 18–40 years, two males and one female) was biopsied from a healthy part of their upper arm at a Russian hospital and provided by Obio LLC (El Segundo, CA). Informed consent was obtained for experimentation with all human subjects. The Ethics Committee for Human Research (Hoyu Co., Ltd., Aichi, Japan) approved this study.
Immunohistochemical staining
The biopsied skin samples were fixed in buffered formalin, embedded in paraffin, and sectioned at 5 μm thick. After the samples were
Expression of HDC in the skin
The epidermis is primarily composed of keratinocytes, which comprise >90% of the epidermal cells; other epidermal cells include melanocytes, Langerhans cells, and Merkel cells. In healthy subjects, HDC-immunoreactive cells were detected around the basal layer of the epidermis (white arrows in Fig. 1a). To examine whether the HDC-immunoreactive cells are keratinocytes, we assessed the immunoreactivities of CK14 (a marker of undifferentiated keratinocytes [18]) and CK10 (a marker of suprabasal
Discussion
This study found HDC-positive and CK14-negative cells in the skin of healthy subjects. The immunohistochemical results of collagen IV revealed that these cells were present in the epidermis. Meanwhile, the immunoreactivity of mast cell tryptase [AA1] was exclusively observed only in the dermis and was not detected in the epidermal HDC-positive cells, suggesting that the epidermal HDC-positive and CK14-negative cells are not mast cells. Furthermore, the cells expressed melanocyte-specific
Conflicts of interest
Y.I. and M.F. are employed by Hoyu Co., Ltd. who financially supported the research.
Declaration of competing interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgments
This work was financially supported by Hoyu Co., Ltd. We would like to thank Ai Kobayashi of Hoyu Co., Ltd. For cell culture and the kind support on tissue staining and Masaki Yoshida of Kracie Home Products, Ltd. For constructive comments on the manuscript.
References (35)
- et al.
Wound healing as on rate of histamine formation
Lancet
(1960) Induction of histidine and ornithine decarboxylase activities in mouse tissues by recombinant interleukin-1 and tumor necrosis factor
Biochem. Pharmacol.
(1989)- et al.
Increase of histidine decarboxylase activity in murine myelomonocytic leukemia cells (WEHI-3B) in parallel to their differentiation into macrophages
Biochim. Biophys. Acta
(1988) - et al.
Expression of 74-kDa histidine decarboxylase protein in a macrophage-like cell line RAW 264.7 and inhibition by dexamethasone
Eur. J. Pharmacol.
(2001) - et al.
Histamine released from epidermal keratinocytes plays a role in α-melanocyte-stimulating hormone-induced itching in mice
Am. J. Pathol.
(2015) - et al.
The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells
Cell
(1982) Structure and biosynthesis of basement membranes
Int. Rev. Connect. Tissue Res.
(1973)- et al.
Mast cell-/basophil-specific transcriptional regulation of human L-histidine decarboxylase gene by CpG methylation in the promoter region
J. Biol. Chem.
(1998) - et al.
Intracellular localization of the 74- and 53-kDa forms of L-histidine decarboxylase in a rat basophilic/mast cell line, RBL-2H3
J. Biol. Chem.
(1998) - et al.
Microphthalmia transcription factor. A sensitive and specific melanocyte marker for MelanomaDiagnosis
Am. J. Pathol.
(1999)