The Expression of Histamine Receptors in Skin Lesions of MRL/MPlpr/ lpr Mice

Abstract

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease accompanied with systemic organs disorder including skin changes. The MRL/MP-lpr/lpr (MRL/l) mouse is a model of human LE. MRL/l mice skin lesions exhibit a decreased activity in histamine-N-methyltransferase (HMT) and impaired histamine metabolism. In order to clarify the role of histamine receptors (HRs) including H1R, H2R and H3R in MRL/l skin lesions, the relationship between HRs and skin lesions was assessed by immunohistochemical staining and RT-PCR methods. The expression of H2R was seen in the non-lesional skin of 2-month-old (mo) MRL/l mice; H2R expression continued for a couple of months, and then decreased in the skin lesions of 5-mo MRL/l mice. In MRL/l skin lesions, a dense mast cell infiltration expressed H2R was seen. In conclusion, an increased expression of H2R in mast cells may be associated with histamine metabolism in skin lesions from MRL/l mice.

The Protective Effects of Ultraviolet A1 Irradiation on Spontaneous Lupus Erythematosus-Like Skin Lesions in MRL/lpr Mice

“…In consistent with the previous study [ 19 ], we could detect massive infiltration of mast cells in the LE-like skin lesions of MRL/lpr mice, compared with nonlesional skins in both nonirradiated and UVA1-irradiated mice. ( Figures 3(b) , 4 ).…”

“…We also examined the expression of the histamine receptors in both the LE-like skin lesion and nonlesional skins of nonirradiated and UVA1-irradiated mice by immunohistochemical and RT-PCR analyses. Similar to our previous results [19], some infiltrating mononuclear cells expressed H2R in the LE-like skin lesions, and the expression of H2R mRNA was significantly up-regulated (data not shown). However, in nonlesional skins of MRL/lpr mice, there was no significant change in H2R mRNA expression between the nonirradiated and UVA1-irradiated mice.…”

“…Several lines of accumulating evidence demonstrated that histamine, a major inflammatory mediator mainly derived from mast cells, was closely related with the development of LE-like skin lesions of MRL/lpr mice through HRs [ 19 , 25 ]. Tachibana et al suggested that the impairment of histamine metabolism in MRL/lpr mice would contribute to the development of LE-like skin lesions [ 25 ].…”

“…The levels of mRNA expression of TNF- α , IFN- γ , IL-4, IL-10, TGF- β , H1R, H2R, and H3R were determined by RT-PCR analyses, as described previously [ 19 – 21 ]. Briefly, the total RNAs were extracted from dorsal skin specimens with Sepazol-RNA I (Nacalai Tesque, Inc., Kyoto, Japan) and reverse transcribed using a SuperScript III First-Strand cDNA Synthesis System (Invitrogen) according to the manufacturer's protocol.…”

“…In the present study, we investigated the effects of UVA1 irradiation on MRL/lpr mice, particularly on their LE-like skin lesions, using a disease prevention model. Simultaneously, we also studied the dermal infiltration of mast cells, histamine receptor (HR) expression [ 19 ] and the mRNA expression of cytokines [ 20 ], which were previously examined in the spontaneous LE-like skin lesions in MRL/lpr mice [ 19 , 20 ].…”