IL-36 Cytokine Expression and Its Relationship with p38 MAPK and NF-κB Pathways in Psoriasis Vulgaris Skin Lesions

Summary： This study examined the correlation of the expression of interleukin-36 （IL-36）, a novel member of interleukin-1 （IL-1） family, with p38 mitogen-activated protein kinase （p38 MAPK） and nu clear factor-kappa B （NF-kB） pathways in psoriasis vulgaris skin lesions. The expression levels of IL-36a, IL-3613, IL-367, phosphorylated p38 MAPK, and NF-id3p65 were detected in the skin tissues of 38 psoriasis patients and 17 healthy control subjects by real-time quantitative reverse transcription po lymerase chain reaction （qRT-PCR） and Western blotting. The cytokine expression levels were com pared between the psoriasis group and the control group. A correlation analysis between cytokine pro teins was performed in the psoriasis group. Results showed that the expression levels of IL-36a, IL-3613, IL-36y, phosphorylated p38 MAPK and NF-rh3p65 in the psoriasis group were Significantly higher than those in the control group （P〈0.001）. In the psoriasis group, the IL-36 cytokine expression was positively correlated with phosphorylated p38 MAPK and NF-kBp65 expression （P〈0.05）. A significant positive correlation was also found between the phosphorylated p38 MAPK and NF-v,.Bp65 expression （P〈0.01）. It was concluded that the increased IL-36 expression is correlated with p38 MAPK and NF-kB pathways in psoriasis vulgaris skin lesions. All the three factors may be jointly involved in the pathogenesis and local inflammatory response of psoriasis.

Protective effect of Jiaweibugan decoction against diabetic peripheral neuropathy

Oxygen free radical damage is regarded as a direct or indirect common pathway associated with diabetic neuropathy and is the main cause of complications in peripheral neuropathies. We speculate that Jiaweibugan decoction has a significant effect in treating diabetic peripheral neuropathy through an anti-oxidative stress pathway. In this study, a diabetic rat model was established by intraperitoneal injection of streptozotocin. Rats were treated with Jiaweibugan decoction via intragastric administration. The levels of malondialdehyde and glutathione, which are indirect indexes of oxidative stress, in serum were determined using a colorimetric method. The expression levels of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase, which are oxidative stress associated factors, in the dorsal root ganglion of spinal $4-6 segments were evaluated by reverse-transcriptase polymerase chain reaction and immunohistochemistry. Results showed that, Jiaweibugan decoction significantly ameliorated motor nerve conduction velocity in diabetic rats, effectively decreased malondialdehyde levels in serum and the expression of nuclear factor kappa B p65 mRNA and p38 mitogen-activated protein kinase mRNA in the dorsa root ganglion, and increased glutathione levels in serum. Therefore, our experimental findings indicate that Jiaweibugan decoction plays an anti-oxidative stress role in the diabetic peripheral neuropathy process, which has a protective effect on peripheral nerve injury.

Pioglitazone ameliorates retinal ischemia/reperfusion injury via suppressing NLRP3 inflammasome activities

AIM：To explore the role of Pioglitazone（Pio） on a mouse model of retinal ischemia/reperfusion（I/R） injury and to elucidate the potential mechanism.METHODS：Retinal ischemia was induced in mice by increasing the intraocular pressure,and Pio was administered 4 h though periocular injection before I/R.The number of cells in the ganglion cell layer（GCL） was counted 7 d after retinal I/R injury.Glial fibrillary acidic protein（GFAP）,nuclear factor-kappa B（NF-κB）,p38,phosphorylated-p38,PPAR-γ,interleukin-1β（IL-1β）,Toll-like receptor 4（TLR4）,NLRP3,cleaved caspase-1,caspase-1 were determined by real-time polymerase chain reaction and Western blotting.RESULTS：Pio promoted the survival of retinal cells in GCL following retinal I/R injury（P〈0.05）.Besides,retinal I/R injury stimulated the expression of GFAP and TLR4,which were partially reversed by Pio treatment（P0.05）.Retinal I/R injury-upregulated expression of NLRP3,cleaved caspase-1,IL-1β was attenuated after Pio treatment（P〈0.05）.Moreover,I/R injury induced activation of NF-κB and p38 were inhibited by Pio treatment（P〈0.05）.CONCLUSION：Pio promotes retinal ganglion cells survival by suppressing I/R-induced activation of TLR4/NLRP3 inflammasomes via inhibiting NF-κB and p38 phosphorylation.

Protective Effect of Hydroxysafflor Yellow A on Inflammatory Injury in Chronic Obstructive Pulmonary Disease Rats

Objective: To investigate the attenuating effect of Hydroxysafflor yellow A(HSYA) on inflammatory injury in chronic obstructive pulmonary disease(COPD). Methods: Rats were randomly assigned to 7 groups according to body weight including normal control group, HSYA blank group(76.8 mg/kg), COPD group, COPD+HSYA(30, 48, 76.8 mg/kg) groups and COPD+dexamethasone(2 mg/kg), 10 in each group. Passive cigarette smoke and intratracheal instil ation of lipopolysaccharides were used to establish a COPD model in rats. Hematoxylin and eosin staining of lung tissue sections was used, real-time polymerase chain reaction(PCR) was used to assay m RNA levels of some cytokines in lung tissues, the cytokines in bronchoalveolar lavage fluid(BALF) were measured by enzyme-linked immunosorbent assay(ELISA), Western blot analysis was used to determine phosphorylated p38 mitogen-activated protein kinase(MAPK) levels in lung tissues, and nuclear factor-κB(NF-κB) p65 protein levels in lung tissues were detected by immunohistochemistry. Results: Lung alveolar septa destruction, alveolus fusion, inflammatory cel infiltration, and bronchiole exudation were observed. These pathological changes were al eviated in the COPD+HSYA group. The m RNA expression of inflammatory factors were significantly increased in lung tissues from COPD rats(all P<0.01) and were inhibited by HSYA. Levels of inflammatory cytokines in BALF of COPD rats were significantly increased(all P<0.01) which were inhibited by HSYA(all P<0.01, 48, 76.8 mg/kg). The levels of p38 MAPK phosphorylation and p65 in lung tissues of COPD rats were significantly increased(al P<0.01) and were suppressed by HSYA(all P<0.01, 48, 76.8 mg/kg). Conclusions: HSYA could alleviate inflammatory cell infiltration and other pathological changes in the lungs of COPD rats. HSYA could inhibit inflammatory cytokine expression, and increase phosphorylation of p38 MAPK and NF-κB p65 in the lungs of COPD rats. The protective mechanism of HSYA to inhibit COPD inflammation might be by attenuating NF-κB and p38 MAPK signal transduction.

有氧运动与饮食干预对肥胖小鼠睾丸氧化应激的影响

目的:通过对肥胖小鼠施加有氧运动与饮食干预,探索运动与饮食干预对肥胖小鼠睾丸氧化应激和p38MAPK-NF-κB通路中的作用。方法:随机将17只C57BL/6J小鼠分为正常饮食组(ND),37只分为高脂饮食组(HFD),高脂饮食脂肪占比40%,喂养12周后,HFD组剔除3只肥胖抵抗小鼠,其余34只肥胖造模成功;随后将ND组分为正常饮食对照组(NC,n=8),正常饮食运动组(NE,n=9),肥胖高脂饮食对照组(OC,n=8),肥胖高脂饮食运动组(OE,n=9),肥胖正常饮食组(ONC,n=8),肥胖正常饮食运动组(ONE,n=9),各组继续饲养8周,其中NE、OE和ONE组以速度20 m/min,60 min/d,6 d/week,进行8周跑台运动,末次运动后36~40 h取血和睾丸组织,ELISA检测血清睾酮和睾丸氧化应激(MDA、T-SOD、T-AOC)水平,RT-PCR和Western blot检测睾丸p38MAPK-NF-κB水平。结果:与NC组比较,OC组小鼠体脂参数、睾丸MDA和睾丸p38MAPK-NF-κB mRNA和蛋白水平明显升高(P<0.01),睾丸SOD、睾丸系数和血睾酮明显降低(P<0.01);NE组小鼠体脂参数明显降低(P<0.05),血清睾酮明显升高(P<0.01)。与OC组比较,OE组小鼠体脂参数、睾丸MDA和睾丸p38MAPK-NF-κB mRNA和蛋白水平明显降低(P<0.05或0.01),睾丸SOD和血睾酮水平明显升高(P<0.01);ONC组小鼠体脂参数、睾丸MDA和睾丸p38MAPK-NF-κB mRNA和蛋白水平明显降低(P<0.01),睾丸SOD水平和睾丸系数明显升高(P<0.05);ONE组小鼠体脂参数、睾丸MDA和睾丸p38MAPK-NF-κB mRNA和蛋白水平明显降低(P<0.01),睾丸SOD、睾丸系数和血睾酮水平明显升高(P<0.01)。结论:肥胖引起小鼠睾丸发生氧化应激,上调睾丸p38MAPK-NF-κB水平,并降低血睾酮水平;运动、饮食和运动×饮食干预均能通过降低体脂,改善睾丸氧化应激,下调睾丸p38MAPK-NF-κB水平。