Muscle-specific deletion of exons 2 and 3 of the IL15RA gene in mice: effects on contractile properties of fast and slow muscles
JOURNAL OF APPLIED PHYSIOLOGY
Authors: O'Connell, Grant; Guo, Ge; Stricker, Janelle; Quinn, LeBris S.; Ma, Averil; Pistilli, Emidio E.
Abstract
Interleukin-15 (IL-15) is a putative myokine hypothesized to induce an oxidative skeletal muscle phenotype. The specific IL-15 receptor alpha subunit (IL-15R alpha) has also been implicated in specifying this contractile phenotype. The purposes of this study were to determine the muscle-specific effects of IL-15R alpha functional deficiency on skeletal muscle isometric contractile properties, fatigue characteristics, spontaneous cage activity, and circulating IL-15 levels in male and female mice. Muscle creatine kinase (MCK)-driven IL-15R alpha knockout mice (mIl15ra(fl/fl)/Cre(+)) were generated using the Cre-loxP system. We tested the hypothesis that IL-15R alpha functional deficiency in skeletal muscle would increase resistance to contraction-induced fatigue, cage activity, and circulating IL-15 levels. There was a significant effect of genotype on the fatigue curves obtained in extensor digitorum longus (EDL) muscles from female mIl15ra(fl/fl)/Cre(+) mice, such that force output was greater during the repeated contraction protocol compared with mIl15ra(fl/fl)/Cre(+) control mice. Muscles from female mIl15ra(fl/fl)/Cre(+) mice also had a twofold greater amount of the mitochondrial genome-specific COXII gene compared with muscles from mIl15ra(fl/fl)/Cre(+) control mice, indicating a greater mitochondrial density in these skeletal muscles. There was a significant effect of genotype on the twitch: tetanus ratio in EDL and soleus muscles from mIl15ra(fl/fl)/Cre(+) mice, such that the ratio was lower in these muscles compared with mIl15ra(fl/fl)/Cre(+) control mice, indicating a pro-oxidative shift in muscle phenotype. However, spontaneous cage activity was not different and IL-15 protein levels were lower in male and female mIl15ra(fl/fl)/Cre(+) mice compared with control. Collectively, these data support a direct effect of muscle IL-15R alpha deficiency in altering contractile properties and fatigue characteristics in skeletal muscles.
IL-15 receptor alpha rs2228059 A > C polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population
MOLECULAR BIOLOGY REPORTS
Authors: Yin, Jun; Wang, Liming; Shi, Yijun; Shao, Aizhong; Tang, Weifeng; Wang, Xu; Zhang, Wenbo; Ding, Guowen; Liu, Chao; Chen, Yijang; Chen, Suocheng; Gu, Haiyong
Abstract
Esophageal cancer is the sixth leading cause of cancer-related deaths worldwide. Esophageal cancer is very aggressive; genetic polymorphisms may explain in part the individual differences in esophageal cancer susceptibility. We conducted a hospital based case-control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin (IL)-15 and IL-15 receptor alpha (IL-15RA) gene on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom-by-design 48-Plex SNPscan(TM) kit. The IL-15RA rs2228059 A > C polymorphism was associated with a decreased risk of ESCC in a recessive genetic model; However, there was no significant association between the other five SNPs and ESCC risk. Stratified analyses indicated a significantly decreased risk of ESCC associated with the IL-15RA rs2228059 A > C polymorphism was evident among male, older, non-smoker, and non-drinker patients. These findings indicated that the functional polymorphism, IL-15RA rs2228059 A > C, might contribute to ESCC susceptibility. However, the statistical power of our study was limited because of the moderate sample size and absence of a validation cohort. Large well-designed studies are warranted to confirm our findings.
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