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The objective of this study was to identify the key changed subtype of T helper cells (Th cells) and their cytokines in pristane-induced arthritis (PIA) in rats. The severity of arthritis was evaluated by body weight, clinical score, the perimeter of ankle and mid-paw and histological assessment of ankle joints. Cytokines of Th1, Th2 and Th17 were determined in the spleen and inguinal lymph nodes at 28 days after pristane injection by real-time qPCR. The mRNA levels of IL-22 receptors, IL-22R1 and IL-22BP, in the spleen were quantified by real-time qPCR. Additionally, IL-22 expression in synovial membrane was detected by Western blotting, and serum IL-22 concentration was determined by ELISA. Correlation between IL-22 concentration and clinical score was analyzed. By screening the cytokines of Th1, Th2 and Th17 expression profile, we found that the mRNA levels of Th17 cytokines were significantly increased in PIA rats. Particularly, a significant increase in the protein expression of IL-22 was determined in synovial membrane and serum from PIA rats, and correlated with clinical score. We conclude that IL-22 expression level was increased and correlated with disease severity, which indicated that IL-22 may play an important role in development of PIA, and was helpful to explorer the pathogenesis of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

The present study aims to investigate the role of liensinine in life-threatened sepsis-associated encephalopathy (SAE) mice and the underlying mechanism. Here, seventy-two mice were divided into six groups, including the control group, SAE group, liensinine-treated group, and three doses of liensinine-treated SAE groups. Lipopolysaccharide triggered cerebrum necrosis and disrupted the integrity and permeability of blood-brain barrier (BBB). While liensinine restored cerebrum structure and improved BBB integrity with upregulated tight junction proteins, decreased evans blue leakage and fibrinogen expression with decreased matrix metalloproteinases 2/9 in serum, thereby reducing BBB permeability. Moreover, lipopolysaccharide triggered cerebrum oxidative stress and inflammation, whereas liensinine enhanced antioxidant enzymes activities and weakened malondialdehyde through nuclear factor erythroid 2-related factor. Meanwhile, liensinine inhibited inflammation by activating inducible nitric oxide synthase. Tunel staining combined with transmission electron microscope indicated that lipopolysaccharide induced cerebrum apoptosis, whereas liensinine blocked apoptosis through decreasing B-cell lymphoma-2 associated X (Bax) expression and cytochrome C (Cyto-c) release, increasing B-cell lymphoma-2 (Bcl-2) expression, blocking apoptosome assembly, inhibiting caspase-3 activation, thereby suppressing intrinsic mitochondria apoptosis. Recovering of inflammatory homeostasis and inhibition of mitochondria apoptosis by liensinine ultimately restored cognitive function in SAE mice. Altogether, liensinine attenuated lipopolysaccharide-induced SAE via modulation of Nrf2-mediated inflammatory biomarkers and mitochondria apoptosis. • Liensinine improves cerebrum morphology and BBB integrity by increasing TJ proteins. • Liensinine reduces SAE mice BBB permeability by decreasing MMP2 and MMP9 activities. • Liensinine restores SAE mice cerebrum redox balance by activating Nrf2/HO-1 pathway. • Liensinine alleviates SAE mice cerebrum inflammation by inhibiting mediator iNOS. • Liensinine alleviates excessive apoptosis and resists cognitive impairment. [ABSTRACT FROM AUTHOR]

Vibrio alginolyticus is an important zoonotic marine pathogenic bacterium. Previous studies on the mechanism of innate immune against V. alginolyticus infection have been limited to aquatic animals, however, how V. alginolyticus activates mammalian immune cells has not been fully clarified. Here, ELISA combined RT-qPCR assays were used to detect the secretion and transcription level of pro-inflammatory cytokines and TLRs during V. alginolyticus infection of mice peritoneal macrophages (PMϕs). Western blotting was used to explore the phosphorylation levels of p38, JNK, ERK, AKT and NF-κB protein. Immunofluorescence assay was used to determine the location of NF-κB protein. Inhibition assay was used to study the role of up-regulated TLR in activated signaling pathways and the role of these pathways in the release of pro-inflammatory cytokines. Our data showed that V. alginolyticus can up-regulate the expression levels of IL-1β, IL-6, IL-12 and TNF-α in PMϕs. In addition, V. alginolyticus stimulation activated the phosphorylation of p38, JNK and ERK were TLR2 heterodimers-dependent, whereas inhibitors of SB203580 (p38), SCH772984 (ERK) and SP600125 (JNK) significantly reduced IL-1β, IL-6, IL-12 and TNF-α production. We further revealed that V. alginolyticus activated the signaling pathways of AKT via TLR2 heterodimers. The inhibitor of MK-2206 2HCl (AKT) negatively regulated the IL-1β, IL-6 and TNF-α release levels. Moreover, V. alginolyticus infection of PMϕs resulted in TLR2 heterodimers-mediated activation of NF-κB and induced translocation of phosphorylated NF-κB protein from the cytoplasm into the nucleus via IκBα degradation. V. alginolyticus induced IL-1β, IL-6, IL-12 and TNF-α release were blocked by the specific NF-κB inhibitor, BAY 11–7082. Taken together, our results suggested that activation of the TLR2 heterodimers-mediated downstream signaling pathways NF-κB, MAPK and AKT is responsible for inflammatory response during Vibrio alginolyticus infection in vitro. • V. alginolyticus activate TLR2-mediated MAPK, AKT and NF-κB pathways in mouse PMϕs. • V. alginolyticus activate MAPK and NF-κB pathways to enhance inflammatory response. • Cytokines levels are negatively regulated by AKT pathway in infected PMϕs. [ABSTRACT FROM AUTHOR]

• SIN protects from alcohol-induced ALI. • SIN reduced oxidative stress by enhancing antioxidant enzyme levels and Nrf2/HO-1. • SIN decreased inflammation by inhibiting NLRP3 inflammasome and Akt/NF-κB pathway. • SIN inhibited apoptotic protein levels and down-regulated MAPK expressions. [ABSTRACT FROM AUTHOR]