interleukin-8 and Muscular-Atrophy

Cytokines secreted in the tumor microenvironment function in cancer cachexia (CC), a common clinicopathological syndrome associated with adipocyte wasting and skeletal muscle atrophy. Extracellular vesicles (EVs) secreted by cancer cells actively engage in inter-tissue communication; EVs and enclosed cytokines are largely undefined in CC adipocytes wasting.. EVs derived from Lewis lung carcinoma (LLC) and colorectal cancer C26 cells were extracted and characterized. Conditioned medium and EVs from cancer cells were applied to 3 T3-L1 adipocytes. Recombinant IL-8, IL-8 neutralizing antibody, CXCR2 and NF-κB inhibitor were examined in functional assays. Lipolysis of adipocytes was monitored by Western blots, Oil red O staining and glycerol assays. Furthermore, LLC and C26 cell lines were established as cachexia model to explore the relevance of IL-8 and NF-κB signaling in CC adipose wasting. Adipose tissues were collected for histology analyses.. LLC and C26 cell-derived EVs induced lipolysis of 3 T3-L1 adipocytes. Specially, Dil-labeled EVs were effectively taken up by 3 T3-L1 adipocytes, which were motivated by the delivered IL-8 to elicit the NF-κB pathway. In comparison, special IL-8 neutralizing antibody relieved that lipolysis of 3 T3-L1 adipocytes induced by EVs together with conditioned medium of LLC and C26 cells, respectively. Consistently, both CXCR2 and NF-κB inhibitors would lessen the phenotype of lipolysis in 3 T3-L1 adipocytes. In the in vivo settings, both LLC and C26-tumor bearing mice had higher serum IL-8 levels as compared to the control groups. Two typical lipolysis markers, PGC1α and UCP1, were also up-regulated in the adipose tissues of LLC and C26-tumor mice groups, respectively.. EVs secreted by LLC and C26 tumor cells would induce adipocyte wasting via extracellular IL-8-mediated NF-κB signaling. Our study pointed out the physiological and therapeutic values of exosomal IL-8 in CC lipolysis.

Topics: Adipocytes; Animals; Antibodies, Neutralizing; Cachexia; Colonic Neoplasms; Culture Media, Conditioned; Cytokines; Interleukin-8; Lipolysis; Lung Neoplasms; Mice; Muscular Atrophy; NF-kappa B; Signal Transduction; Tumor Microenvironment

Chronic obstructive pulmonary disease (COPD) skeletal muscle dysfunction is a prevalent malady that significantly affects patients' prognosis and quality of life. Although the study of this disease has attracted considerable attention, a definite animal model is yet to be established. This study investigates whether smoke exposure could lead to the development of a COPD skeletal muscle dysfunction model in rats.. Sprague Dawley rats were randomly divided into model (MG, n = 8) and control groups (CG, n = 6). The MG was exposed to cigarette smoke for 16 weeks while the CG was not. The body weight and forelimb grip strength of rats were monitored monthly. The pulmonary function and the strength of tibialis anterior muscle were assessed in vitro and compared after establishing the model. The histological changes in lung and gastrocnemius muscles were observed. The expressions of interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α were detected by ELISA, while the expressions of Atrogin-1 and MuRF1 in the gastrocnemius muscle were determined by Western blotting.. Smoke exposure slowly increases the body weight and forelimb grip strength of MG rats, compared to CG rats. However, it significantly decreases the pulmonary ventilation function and the skeletal muscle contractility of the MG in vitro. Histologically, the lung tissues of MG show typical pathological manifestations of emphysema, while the skeletal muscles present muscular atrophy. The expressions of IL-6, IL-8, and TNF-α in MG rats are significantly higher than those measured in CG rats. Increased levels of Atrogin-1 and MuRF1 were also detected in the gastrocnemius muscle tissue of MG.. Progressive smoking exposure decreases the contractile function of skeletal muscles, leading to muscular atrophy. It also increases the expressions of inflammatory and muscle protein degradation factors in COPD rats. This indicates that smoke exposure could be used to establish a COPD skeletal muscle dysfunction model in rats.

Topics: Animals; Cigarette Smoking; Disease Models, Animal; Interleukin-6; Interleukin-8; Lung; Male; Muscle Contraction; Muscle Proteins; Muscle, Skeletal; Muscular Atrophy; Pilot Projects; Pulmonary Disease, Chronic Obstructive; Pulmonary Emphysema; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Disuse and/or local inflammation in the muscle cannot be excluded as potential influences for the decreased muscle force in patients hospitalised due to an acute chronic obstructive pulmonary disease (COPD) exacerbation. This study aims to compare expression levels of markers of disuse (insulin-like growth factor-1 (IGF-I), MyoD and myogenin) and inflammation [interleukin-6 (IL-6), IL-8 and tumour necrosis factor-alpha (TNF-alpha)] in the muscle of hospitalised and stable COPD patients and healthy elderly.. Muscle biopsies (m. vastus lateralis) were taken in 14 hospitalised COPD patients (aged 68 +/- 8), 11 clinically stable COPD patients (aged 68 +/- 9) and seven healthy subjects (aged 70 +/- 7) to analyse local mRNA expression levels of IL-6, IL-8, TNF-alpha, IGF-I and protein expression levels of IGF-I, MyoD and myogenin. Relationships of these expression levels with lung and skeletal muscle function were investigated.. IGF-I mRNA and MyoD protein levels were significantly lower in hospitalised patients compared to healthy subjects. MyoD protein levels were positively related to quadriceps force. Muscle IL-6 and IL-8 expression in hospitalised patients was similar compared to stable patients and healthy subjects and was not related to expression levels of muscle markers of disuse or quadriceps force. Muscle TNF-alpha and myogenin were not detected.. Decreased expression levels of muscle IGF-I and MyoD in hospitalised patients suggest a potential influence of disuse in the increased muscle weakness during an acute COPD exacerbation. This study did not find any evidence supporting local inflammation via IL-6, IL-8 and/or TNF-alpha in the vastus lateralis muscle of COPD patients.

Topics: Adult; Aged; Biomarkers; Cross-Sectional Studies; Female; Humans; Insulin-Like Growth Factor I; Interleukin-6; Interleukin-8; Male; Middle Aged; Muscular Atrophy; MyoD Protein; Pulmonary Disease, Chronic Obstructive; Quadriceps Muscle; RNA, Messenger; Tumor Necrosis Factor-alpha