Influence of the TLR4-mediated p38MAPK signaling pathway on chronic intermittent hypoxic-induced rat's oxidative stress and inflammatory cytokines in rats.

OBJECTIVE: To investigate the influence of the TOLL-like receptor 4 (TLR4)-mediated p38MAPK signaling pathway on chronic intermittent hypoxic (CIH)-induced oxidative stress and inflammatory cytokines in rats. MATERIALS AND METHODS: A total of 120 healthy male Sprague Dawley (SD) rats, aged between 8-10 weeks, were randomly divided into 9 groups (normoxia control group, CIH 2 weeks group, CIH 4 weeks group, CIH 6 weeks group, CIH 8 weeks group, CIH 6 weeks + p38MAPK receptor inhibit group, CIH 6 weeks + Tempol group, CIH 8 weeks + p38MAPK receptor inhibitor group and CIH 8 weeks + Tempol group). The expression of TLR4 and p38MAPK in the adipose tissue was evaluated, as well as the level of serum oxidative stress markers (SOD, TRx-1, MDA) and inflammatory cytokines (adiponectin, TNF-α, hsCRP and IL-6). RT-PCR and Western-blot were conducted to detect the expression of TLR4 and p38MAPK mRNA. RESULTS: With increased hypoxia, the levels of SOD and adiponectin in the serum of the CIH group decreased significantly, and the levels of TNF-α, hsCRP, IL-8 and IL-6 in serum increased significantly. After the intervention of antioxidant Tempol and p38MAPK inhibitor SB203580, SOD increased significantly but with significant MDA reduction. The levels of TNF-α, hsCRP, IL-8 and IL-6 in serum significantly decreased. The results of RT-PCR and Western-Blot indicated that the P-p38 and TLR4 proteins related to the MAPK pathway were expressed in rat adipose tissue. With the hypoxia intensity, expression of P-p38 decreased after initially increasing. The expression of TLR4 showed a continuously growing trend. After Tempol treatment, the expression of p38MAPK protein decreased, and the expression of TLR4 did not change significantly, indicating the inhibiting effect of Tempol on p38MAPK, without a significant inhibiting effect on TLR4. CONCLUSIONS: The TLR4-mediated p38MAPK signaling pathway was active in adipose tissue and the expression of the corresponding molecules increased as the duration of intermittent hypoxia increased. The expression of TLR4 and p38MAPK components regulated the level of oxidative stress and inflammatory cytokines; the application of p38MAPK inhibitors and antioxidant free radical scavengers improved the levels of oxidative stress and inflammatory cytokines.

Could omega-3 fatty acids a therapeutic treatment of the immune-metabolic consequence of intermittent hypoxia in obstructive sleep apnea?

Obesity and Obstructive sleep Apnea (OSA) seems to bi-directional; obesity itself increases the risk of OSA, but on the other hand, OSA may also predispose the individuals to weight gain, both obesity and OSA share a common immune-metabolic link state which have a synergistic effect on the activation of inflammation, insulin resistance and dyslipidemia, and cardiovascular disease. The Immune-metabolic role of omega-3 fatty acids Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA), which capable of modulating both metabolic and immune process, which may decrease pro-inflammatory cytokines, insulin resistance, and dyslipidemia. To date, no study in humans suffering from OSA and omega-3 fatty acids has been performed. Hence, the objective of this review aimed to discussing the link between immune-metabolic consequences related to intermittent hypoxia and does Omega-3 fatty acids a therapeutic treatment for co-morbidity associated with obstructive sleep apnea.

Sleep apnea: a model for studying cytokines, sleep, and sleep disruption.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder, characterized by repeated disruptions of breathing during sleep. The sleep fragmentation and accompanying hypoxemia lead to many negative consequences including cardiac arrhythmias, nocturnal hypertension, confusion, cognitive impairment, daytime sleepiness, as well as depressive symptoms. From the perspective of psychoneuroimmunology (PNI), OSA holds promise as a model for studying sleep and cytokines because of its many relevant characteristics, including neuroimmune interactions, mood changes, and behaviors that directly affect the course of the disorder. In this minireview we briefly summarize the existing literature on cytokines and sleep and then discuss work on cytokines and OSA. We believe that the study of OSA presents researchers with an excellent opportunity to tease apart the many complex and interwoven components of sleep that are relevant to PNI.