L-Arginine stimulates proliferation and prevents endotoxin-induced death of intestinal cells.
This study tested the hypothesis that L-arginine (Arg) may stimulate cell proliferation and prevent lipopolysaccharide (LPS)-induced death of intestinal cells. Intestinal porcine epithelial cells (IPEC-1) were cultured for 4 days in Arg-free Dulbecco's modified Eagle's-F12 Ham medium (DMEM-F12) containing 10, 100 or 350 microM Arg and 0 or 20 ng/ml LPS. Cell numbers, protein concentrations, protein synthesis and degradation, as well as mammalian target of rapamycin (mTOR) and Toll-like receptor 4 (TLR4) signaling pathways were determined. Without LPS, IPEC-1 cells exhibited time- and Arg-dependent growth curves. LPS treatment increased cell death and reduced protein concentrations in IPEC-1 cells. Addition of 100 and 350 microM Arg to culture medium dose-dependently attenuated LPS-induced cell death and reduction of protein concentrations, in comparison with the basal medium containing 10 microM Arg. Furthermore, supplementation of 100 and 350 microM Arg increased protein synthesis and reduced protein degradation in both control and LPS-treated IPEC-1 cells. Consistent with the data on cell growth and protein turnover, addition of 100 or 350 microM Arg to culture medium increased relative protein levels for phosphorylated mTOR and phosphorylated ribosomal protein S6 kinase-1, while reducing the relative levels of TLR4 and phosphorylated levels of nuclear factor-kappaB in LPS-treated IPEC-1 cells. These results demonstrate a protective effect of Arg against LPS-induced enterocyte damage through mechanisms involving mTOR and TLR4 signaling pathways, as well as intracellular protein turnover.
Tan
Bie
B
Hunan Engineering Technology Research Center of Healthy Animal Husbandry and Laboratory for Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, 410125, Hunan, China.
Yin
Yulong
Y
Kong
Xiangfeng
X
Li
Peng
P
Li
Xilong
X
Gao
Haijun
H
Li
Xinguo
X
Huang
Ruilin
R
Wu
Guoyao
G
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D016923:Cell Death; D002460:Cell Line; D049109:Cell Proliferation; D019610:Cytoprotection; D019587:Dietary Supplements; D020895:Enterocytes / Q000166:cytology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D015398:Signal Transduction; D013552:Swine; D058570:TOR Serine-Threonine Kinases; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011506:Proteins; D051197:Toll-Like Receptor 4; D001120:Arginine; D017346:Protein Serine-Threonine Kinases; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases; C448901:ribosomal protein S6 kinase, 70kD, polypeptide 1