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To conduct an in vitro investigation into the effect of different concentrations of levocetirizine hydrochloride on the growth of human dermal papilla cells (hDPCs) the underlying mechanisms involved.hDPCs were cultured in Dulbecco's Modified Eagle Medium (DMEM) containing different concentrations of levocetirizine hydrochloride for 48 h. The growth of hDPCs was observed by immunofluorescence staining, and the cell proliferation was detected by MTT assay. After the hDPCs were cultured in DMEM containing 1, 10, 100, 1,000, and 10,000 ng/mL levocetirizine hydrochloride for 48 h, the mRNA expressions of cyclooxygenase 2 (COX-2), prostaglandin D2 synthase (PTGDS), prostaglandin E2 (PGE2), prostaglandin F2α (PGF2α), G protein-coupled receptor 44 (GPR44), protein kinase B (AKT), and glycogen synthase kinase 3β (GSK3β) were determined by real-time fluorescence-based quantitative polymerase chain reaction (PCR), and the protein expressions of PTGDS, phosphorylated protein kinase B (pAKT), and phosphorylated glycogen synthase kinase 3β (pGSK3β) were detected by Western blotting. After the hDPCs were cultured in DMEM containing 1, 10, 100, 1,000, 10,000 ng/mL levocetirizine hydrochloride for 24 h, the secretion levels of prostaglandin D2 (PGD2) and PGD2 receptor (PGD2R) in the culture supernatant were determined by enzyme-linked immunosorbent assay (ELISA). One-way analysis of variance (ANOVA) was performed using SPSS 17.0 software, and the LSD-t test was used for pairwise comparisons.Immunofluorescence staining showed that hDPCs in the 100 ng/mL group grew well, with over 90% confluency. Methyl thiazolyl tetrazolium (MTT) method showed that the proliferation rate of hDPCs significantly differed between different levocetirizine hydrochloride groups and the blank control group (F=42.22, P0.05), while the proliferation rate was significantly higher in the 100 ng/mL group (115.80%±5.10%) than in the blank control group (100%) (t=28.26, P0.05). The relative mRNA expressions of COX-2, PGF2a, PTGDS, GPR44, and AKT showed significant differences in different levocetirizine hydrochloride groups (the F values were 1.97, 3.66, 2.17, 2.66, and 7.32, respectively; all P0.05), whereas the mRNA expressions of PGE2 and GSK3β showed no significant difference (F=0.87, F=1.19, respectively; both P0.05). The mRNA expressions of COX-2, PTGDS, and GPR44 in the 100 ng/mL group (0.840.08, 0.810.10, and 0.85±0.09, respectively) were significantly lower than those in the blank control group (t=1.97, t=2.17, and t=2.65, respectively; all P0.05), whereas the mRNA expressions of PGF2α and AKT in the 100 ng/mL group (1.96±0.25 and 1.74±0.32, respectively) were significantly higher than those in the blank control group (t=3.662 and t=7.325, respectively; both P0.05). There were significant differences in the levels of PTGDS, pAKT, pGSK3β, PGD2, and PGD2R proteins between the different levocetirizine hydrochloride groups (the F values were 11.84, 3.89, 4.07, 66.15, and 44.33, respectively). The protein expressions of PTGDS, PGD2, and PGD2R in the 100 ng/mL group (0.32±0.05, 141.62±5.44, and 215.08±9.55, respectively) were significantly lower than those in the blank control group (0.73±0.06, 180.08±6.15, and 273.24±3.18, respectively) (the t values were 5.66, 45.07, and 92.05, respectively; all P0.05), whereas the protein expressions of pAKT and pGSK3β in the 100 ng/mL group (0.59±0.05 and 0.46±0.03, respectively) were significantly higher than those in the blank control group (0.46±0.02 and 0.35±0.042, respectively) (t=16.59, t=7.73, respectively; both P0.05).Levocetirizine hydrochloride may promote the growth and proliferation of hDPC in vitro by inhibiting the PGD2-GPR44 pathway and activating the AKT signaling pathway.

Mutations in TIE2/TEK gene have been identified as the major cause for cutaneomucosal venous malformations (VMCM) that were previously reported to occur in Caucasian families. We report here for the first time a Chinese VMCM family of 19 affected individuals in five generations with multiple vascular lesions on their oral mucosa and extremities. Histological analyses showed that the lesions comprised of irregular vascular spaces with a continuous layer of endothelial cells and variable smooth muscle cells. Although these VMCM characters were consistent with those in Caucasian families, difference was observed in hyperplastic SMC layer and vascular walls. Haplotype analyses and DNA sequencing indicated that both the mutation-associated haplotype and a R849W (c.2545C>T) change of the TIE2 gene cosegregated perfectly with the VMCM phenotype. This result suggested that, like those in Caucasian families, the R849W mutation in TIE2 could be one of the major causes for VMCM in Asian families.

Toll-like receptors (TLRs) are pattern-recognition receptors and have a critical role in both innate and adaptive responses to tissue injury. Our previous study showed that wound healing was impaired in TLR3-deficient mice. In this study, we investigated the capacity of the TLR3 agonist polyriboinosinic-polyribocytidylic acid (poly(I:C)) to promote the healing of skin wounds in humans and mice. We found that topical application with poly(I:C) accelerated the closure of wounds in patients with laser plastic surgery. In a mouse model, topical application of poly(I:C) markedly enhanced re-epithelialization, granulation, and neovascularization required for wound closure. Further studies revealed that poly(I:C) treatment resulted in enhanced recruitment of neutrophils and macrophages in association with upregulation of a chemokine, macrophage inflammatory protein-2 (MIP-2/CXCL2), in the wounds. The effect of poly(I:C) was abolished in TLR3-deficient mice or by treatment with MIP-2/CXCL2-neutralizing antibodies. These results suggest a potential therapeutic value of the TLR3 activator poly(I:C) for wound healing.