ABSTRACT
Objective To investigate the effects of triptolide on the expression of a series of proteins associated with interferon-γ (IFN-γ)signaling in HaCaT keratinocytes.Methods After pretreatment with difrerent dosages of triptolide(10-10-10-7 mol/L),HaCaT cells were stimulated by recombinant human IFN-γ(rhIFN-γ,500 U/mL)for various periods followed by the collection of cells.Then,total protein was extracted from these cells and subjected to Western blotting for the detection of expression of interferon-γ receptor α(IFN-γRα),phosphorylated Janus kinase 2(pJAK2)and suppressor of cytokine signaling (SOCS1).Results Triptolide at the concentrations of 10-8 mol/L and 10-7 mol/L significantly inhibited the IFN-γRα expression upregulated by rhIFN-γ(both P＜0.05).The expression of pJAK2 induced bv rhIFN-γ was also suppressed by triptolide at the concentrations of 10-9 moI/L and 10-8 mol/L(both P＜0.05).The inhibition of triptolide on IFN-γRα and pJAK2 expression was dose-dependent and the 50%inhibitory concentrations(IC50 value)were 1.37×10-8 mol/L and 2.83×10-9 mol/L,respectively.On the contrary,triptolide upregulated the expression of SOCS1 stimulated by rhIFN-γ at the concentrations of 10-10,10-9 and 10-8 mol/L(P＜0.05,0.05,0.01,respectively)with the 50%effective dosage(ED50 value)at 3.32 × 10-11 mol/L.Conclusions By inhibiting the expression of IFN-γRα as well as phosphorylation of JAK2 and upregulating the expression of SOCS1,triptolide inhibits the phosphorylation of STAT-1,resulting in the inhibition of genetic transcription of multiple inflammatory factors induced by IFN-γ signaling in HaCaT keratinocytes,and the inhibition probably contributes to the efficacy of triptolide in the treatment of IFN-γ-dependent inflammatory skin disorders,such as psoriasis.
ABSTRACT
Objective To investigate the effects of 13-hexyl-berbefine hydroehlofide (HB-13) and 13-hexyl-paimatine hydrochloride (HP-13) on the activation of nuclear factor-kappa B (NF-kB) and phosphorylation of p38 mitogen-activated protein kinase (MAPK) in a human keratinocyte cell line, HaCaT stimulated by tumor necrosis factor alpha (TNF-α). Methods HaCaT cells were cultured in the presence of various concentrations (0.39, 0.78, 1.56 μg/mL) of HB-13 or HP-13 for 120 minutes followed by the stimulation with recombinant human TNF-α for 120 minutes (in phosphorylatEd-IkB-α test) or 15 minutes (in phosphorylated-p38 test). Then, HaCaT cells were disrupted, total protein was extracted, and the expressions of phosphorylated I B-α and phosphorylated p38 were detected with Western blot. HaCaT cells receiving neither pretreatment nor stimulation served as blank control, untreated HaCaT cells stimulated by rhTNF-α as stimulator control, and HaCaT cells pretreated with turmeric root tuber and stimulated by rhTNF-α as positive control. Results From 0.39 to 1.56 μg/mL, both HB-13 and HP-13 significantly inhibited the expression of p-IkB-α in HaCaT cells stimulated by rhTNF-α, and a nonsignificant dose-dependent trend was observed for their inhibitory effect, with the ICo value being 0.441 μg/mL for I-IB-13 (r = -0.990, n = 3, P > 0.05) and 0.832 μg/mL for HP-13 (r = -0.992, n = 3, P > 0.05). In contrast, neither 1-113-13 nor HP-13 within the experiment concentration range had a significant effect on the expression of p-p38 in HaCaT cells stimulated by rhTNF-α (P > 0.05). Conclusions Within the experimental concentration range, both HB-13 and HP-13 can inhibit the activation of NF-kB in HaCaT cells induced by TNF-α signal, but neither of them suppress the phosphorylation of p38MAPK induced by TNF-α signal in HaCaT cells.
ABSTRACT
Objective To analyse the clinical and therapeutic features as well as laboratory findings in bullous pemphigoid with non-bullous lesions as initial manifestation. Methods Clinical data on 34 cases of bullous pemphigoid with non-bullous lesions as initial manifestation were retrospectively analyzed. Results The male to female ratio was 1.83 :1, with a mean age of onset at 59.79±15.63 years. Before typical bullae appeared, patients presented with erythema, papules, papulovesicles' plaques" wheals, nodules,or erythema muitiforme-like lesions, with the most common lesions being erythematous papules and plaques (occumng in 35.29% of these patients). Conclusions Among these patients, nearly 1/3 displayed various skin lesions at the onset; simultaneous erythematous papules and plaques are the most common initial manifestation.