Association of <scp>HSP</scp>22 with <scp>mTOR</scp> in osteoblasts: regulation of <scp>TNF</scp>‐α‐stimulated <scp>IL</scp>‐6 synthesis

Sepsis-induced myocardial dysfunction (SIMD) is ubiquitous in septic shock patients and is associated with high morbidity and mortality rates. Heat shock protein 22 (Hsp22), which belongs to the small HSP family of proteins, is involved in several biological functions. However, the function of Hsp22 in lipopolysaccharide (LPS)-induced myocardial injury is not yet established. This study was aimed at investigating the underlying mechanistic aspects of Hsp22 in myocardial injury induced by LPS. In this study, following the random assignment of male C57BL/6 mice into control, LPS-treated, and LPS + Hsp22 treated groups, relevant echocardiograms and staining were performed to scrutinize the cardiac pathology. Plausible mechanisms were proposed based on the findings of the enzyme-linked immunosorbent assay and Western blotting assay. A protective role of Hsp22 against LPS-induced myocardial injury emerged, as evidenced from decreased levels of creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and enhanced cardiac function. The post-LPS administration-caused spike in inflammatory cytokines (IL-1β, IL-6, TNF-α and NLRP3) was attenuated by the Hsp22 pre-treatment. In addition, superoxide dismutase (SOD) activity and B-cell lymphoma-2 (Bcl2) levels were augmented by Hsp22 treatment resulting in lowering of LPS-induced oxidative stress and cardiomyocyte apoptosis. In summary, the suppression of LPS-induced myocardial injury by Hsp22 overexpression via targeting of inflammation, oxidative stress, and apoptosis in cardiomyocytes paves the way for this protein to be employed in the therapy of SIMD.

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Icaritin inhibits lung cancer-induced osteoclastogenesis by suppressing the expression of IL-6 and TNF-a and through AMPK/mTOR signaling pathway

Zhao

Lin

Jiang

et al. 2020

Anti-Cancer Drugs

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Bone metastasis is one of the common phenomena in the late stage of lung cancer. Inhibition of bone metastasis can improve the survival of lung cancer patients. However, the current drugs for the treatment of bone metastasis have shown little effect on overall survival. Therefore, there is an urgent necessity to identify novel drugs capable of preventing and treating bone metastasis of lung cancer. Our study determined that icaritin (ICT) can inhibit lung cancer-mediated osteoclastogenesis and induce the apoptosis of osteoclasts. Exposure to ICT increased the activation of adenosine 5’-monophosphate-activated protein kinase (AMPK), reduced the activation of mammalian target of rapamycin (mTOR) and decreased the expression of bcl-2. The bioactivity of ICT on osteoclastogenesis was associated with the regulation of the AMPK/mTOR signaling pathway. Blocking AMPK significantly increased osteoclast differentiation, decreased osteoclast apoptosis and canceled the effects of ICT on the phosphorylation of AMPK as well as the inhibition of mTOR and bcl-2. Furthermore, ICT decreased the levels of IL-6 and TNF-α in osteoclasts, while the AMPK inhibitor compound C significantly abolished the inhibitory effects of ICT on IL-6 and TNF-α. Thus, the present study demonstrated that ICT may be a potential natural agent for the treatment of bone metastasis in patients with lung cancer.

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Association of HSP22 with mTOR in osteoblasts: regulation of TNF‐α‐stimulated IL‐6 synthesis

Cited by 4 publications

References 41 publications

The Role of IL-6, IL-10, and TNF-α in Ocular GVHD Following Allogeneic Transplantation

The Role of IL-6, IL-10, and TNF-α in Ocular GVHD Following Allogeneic Transplantation

Hsp22 ameliorates lipopolysaccharide-induced myocardial injury by inhibiting inflammation, oxidative stress, and apoptosis

Icaritin inhibits lung cancer-induced osteoclastogenesis by suppressing the expression of IL-6 and TNF-a and through AMPK/mTOR signaling pathway

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