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Human β-defensin 2 (hBD-2) is a potent antimicrobial peptide that participates in defense against invading bacteria. We recently showed that bacterial components and histamine, through histamine H4 receptor (H4R), are involved in the pathogenesis of the potentially malignant lesion, oral lichen planus (OLP). However, the underlying mechanisms remain unknown. We, therefore, investigated the role of hBD2–histamine crosstalk signaling in promoting OLP pathology. Biopsies from OLP and oral tongue squamous cell carcinoma (OTSCC) patients, and healthy controls were used. Two OTSCC cell lines and normal human oral keratinocytes (HOKs) were used. HBD-2 and other targets were mapped by immunostaining and analyzed by ImageJ2 software. The highly sensitive droplet-digital PCR technology and qRT-PCR were utilized to study the clinically derived and in vitro samples, respectively. H4R was challenged with the specific agonist HST-10 and inverse agonist ST-1007. HBD-2 was highly induced in OLP lesions. In contrast, hBD2 expression was attenuated in OTSCC tissues, while very low levels of hBD-2 messenger RNA (mRNA) were observed in OTSCC cells. Together with tumor necrosis factor-α (TNF-α), histamine upregulated hBD-2 mRNA expression in HOKs. Activation of H4R seems to modulate the expression of epithelial hBD-2. These findings suggest the involvement of hBD-2 in the pathogenesis of OLP and may, thus, be harnessed for therapeutic interventions in OLP

Background Systemic lupus erythematosus (SLE) is a complex genetic disease; the histamine H4 receptor (HRH4) has been shown to be related to different kinds of autoimmune disorders; and copy number variations (CNVs) have been found to be associated with various types of diseases. Objectives To explore a possible association between HRH4 (formerly H4R) CNVs and the risk of SLE. Methods Genomic DNA and RNA from 340 patients with SLE and 392 healthy controls were extracted, and CNVs and mRNA levels of HRH4 were examined. Results The expression of HRH4 mRNA was significantly increased in patients with SLE compared with controls. Amplification of HRH4 copy numbers significantly increased the risk of SLE [P<0·001, odds ratio (OR) 2·26, 95% confidence interval (CI) 1·50-3·40]. HRH4 amplifications also positively correlated with the incidence of arthritis (P = 0·019, OR 1·96, 95% CI 1·11-3·47), and proteinuria (P<0·001, OR 2·95, 95% CI 1·73-5·00) and antinuclear antibody abnormalities (P<0·001, OR 2·97, 95% CI 1·66-5·33). Deletions of HRH4 copy numbers were protective against proteinuria (P = 0·03, OR 0·50, 95% CI 0·26-0·94). Conclusion CNVs of the HRH4 gene are associated with SLE. © 2010 British Association of Dermatologists.

Background Systemic lupus erythematosus (SLE) is a complex genetic disease; the histamine H4 receptor (HRH4) has been shown to be related to different kinds of autoimmune disorders; and copy number variations (CNVs) have been found to be associated with various types of diseases. Objectives To explore a possible association between HRH4 (formerly H4R) CNVs and the risk of SLE. Methods Genomic DNA and RNA from 340 patients with SLE and 392 healthy controls were extracted, and CNVs and mRNA levels of HRH4 were examined. Results The expression of HRH4 mRNA was significantly increased in patients with SLE compared with controls. Amplification of HRH4 copy numbers significantly increased the risk of SLE [P<0·001, odds ratio (OR) 2·26, 95% confidence interval (CI) 1·50-3·40]. HRH4 amplifications also positively correlated with the incidence of arthritis (P = 0·019, OR 1·96, 95% CI 1·11-3·47), and proteinuria (P<0·001, OR 2·95, 95% CI 1·73-5·00) and antinuclear antibody abnormalities (P<0·001, OR 2·97, 95% CI 1·66-5·33). Deletions of HRH4 copy numbers were protective against proteinuria (P = 0·03, OR 0·50, 95% CI 0·26-0·94). Conclusion CNVs of the HRH4 gene are associated with SLE. © 2010 British Association of Dermatologists.

Background Systemic lupus erythematosus (SLE) is a complex genetic disease; the histamine H4 receptor (HRH4) has been shown to be related to different kinds of autoimmune disorders; and copy number variations (CNVs) have been found to be associated with various types of diseases. Objectives To explore a possible association between HRH4 (formerly H4R) CNVs and the risk of SLE. Methods Genomic DNA and RNA from 340 patients with SLE and 392 healthy controls were extracted, and CNVs and mRNA levels of HRH4 were examined. Results The expression of HRH4 mRNA was significantly increased in patients with SLE compared with controls. Amplification of HRH4 copy numbers significantly increased the risk of SLE [P<0·001, odds ratio (OR) 2·26, 95% confidence interval (CI) 1·50-3·40]. HRH4 amplifications also positively correlated with the incidence of arthritis (P = 0·019, OR 1·96, 95% CI 1·11-3·47), and proteinuria (P<0·001, OR 2·95, 95% CI 1·73-5·00) and antinuclear antibody abnormalities (P<0·001, OR 2·97, 95% CI 1·66-5·33). Deletions of HRH4 copy numbers were protective against proteinuria (P = 0·03, OR 0·50, 95% CI 0·26-0·94). Conclusion CNVs of the HRH4 gene are associated with SLE. © 2010 British Association of Dermatologists.