PMID- 26057332 OWN - NLM STAT- MEDLINE DCOM- 20160602 LR - 20220311 IS - 1557-7465 (Electronic) IS - 1079-9907 (Linking) VI - 35 IP - 9 DP - 2015 Sep TI - Regulation of Granulocyte Colony-Stimulating Factor and Its Receptor in Skeletal Muscle is Dependent Upon the Type of Inflammatory Stimulus. PG - 710-9 LID - 10.1089/jir.2014.0159 [doi] AB - The cytokine granulocyte colony-stimulating factor (G-CSF) binds to its receptor (G-CSFR) to stimulate hematopoietic stem cell mobilization, myelopoiesis, and the production and activation of neutrophils. In response to exercise-induced muscle damage, G-CSF is increased in circulation and G-CSFR has recently been identified in skeletal muscle cells. While G-CSF/G-CSFR activation mediates pro- and anti-inflammatory responses, our understanding of the role and regulation in the muscle is limited. The aim of this study was to investigate, in vitro and in vivo, the role and regulation of G-CSF and G-CSFR in skeletal muscle under conditions of muscle inflammation and damage. First, C2C12 myotubes were treated with lipopolysaccharide (LPS) with and without G-CSF to determine if G-CSF modulates the inflammatory response. Second, the regulation of G-CSF and its receptor was measured following eccentric exercise-induced muscle damage and the expression levels we investigated for redox sensitivity by administering the antioxidant N-acetylcysteine (NAC). LPS stimulation of C2C12 myotubes resulted in increases in G-CSF, interleukin (IL)-6, monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNFalpha) messenger RNA (mRNA) and an increase in G-CSF, IL-6, and MCP-1 release from C2C12 myotubes. The addition of G-CSF following LPS stimulation of C2C12 myotubes increased IL-6 mRNA and cytokine release into the media, however it did not affect MCP-1 or TNFalpha. Following eccentric exercise-induced muscle damage in humans, G-CSF levels were either marginally increased in circulation or remain unaltered in skeletal muscle. Similarly, G-CSFR levels remained unchanged in response to damaging exercise and G-CSF/G-CSFR did not change in response to NAC. Collectively, these findings suggest that G-CSF may cooperate with IL-6 and potentially promote muscle regeneration in vitro, whereas in vivo aseptic inflammation induced by exercise did not change G-CSF and G-CSFR responses. These observations suggest that different models of inflammation produce a different G-CSF response. FAU - Wright, Craig Robert AU - Wright CR AD - 1 Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University , Burwood, Victoria, Australia . FAU - Brown, Erin Louise AU - Brown EL AD - 1 Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University , Burwood, Victoria, Australia . FAU - Della Gatta, Paul A AU - Della Gatta PA AD - 1 Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University , Burwood, Victoria, Australia . FAU - Fatouros, Ioannis G AU - Fatouros IG AD - 2 Department of Physical Education and Sport Sciences, Democritus University of Thrace , Komotini, Greece . AD - 3 The Institute of Human Performance and Rehabilitation, Center for Research and Technology-Thessaly , Trikala, Greece . FAU - Karagounis, Leonidas G AU - Karagounis LG AD - 4 Nestle Research Center , Nestec Ltd., Lausanne, Switzerland . AD - 5 School of Physical Education and Sport Sciences, University of Thessaly , Karies, Trikala, Greece . FAU - Terzis, Gerasimos AU - Terzis G AD - 6 Athletics Laboratory, School of Physical Education and Sports Science, University of Athens , Athens, Greece . FAU - Mastorakos, Georgios AU - Mastorakos G AD - 7 Endocrine Unit, Second Department of Obstetrics and Gynecology, Athens University Medical School , Athens, Greece . FAU - Michailidis, Yannis AU - Michailidis Y AD - 2 Department of Physical Education and Sport Sciences, Democritus University of Thrace , Komotini, Greece . FAU - Mandalidis, Dimitris AU - Mandalidis D AD - 6 Athletics Laboratory, School of Physical Education and Sports Science, University of Athens , Athens, Greece . FAU - Spengos, Kontantinos AU - Spengos K AD - 8 The 1st Department of Neurology, University of Athens , School of Medicine, Eginition Hospital, Athens, Greece . FAU - Chatzinikolaou, Athanasios AU - Chatzinikolaou A AD - 2 Department of Physical Education and Sport Sciences, Democritus University of Thrace , Komotini, Greece . FAU - Methenitis, Spiros AU - Methenitis S AD - 6 Athletics Laboratory, School of Physical Education and Sports Science, University of Athens , Athens, Greece . FAU - Draganidis, Dimitrios AU - Draganidis D AD - 2 Department of Physical Education and Sport Sciences, Democritus University of Thrace , Komotini, Greece . FAU - Jamurtas, Athanasios Z AU - Jamurtas AZ AD - 3 The Institute of Human Performance and Rehabilitation, Center for Research and Technology-Thessaly , Trikala, Greece . AD - 5 School of Physical Education and Sport Sciences, University of Thessaly , Karies, Trikala, Greece . FAU - Russell, Aaron Paul AU - Russell AP AD - 1 Centre for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University , Burwood, Victoria, Australia . LA - eng PT - Journal Article DEP - 20150609 PL - United States TA - J Interferon Cytokine Res JT - Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research JID - 9507088 RN - 0 (Antioxidants) RN - 0 (CCL2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (IL6 protein, human) RN - 0 (Interleukin-6) RN - 0 (Lipopolysaccharides) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Granulocyte Colony-Stimulating Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - 143011-72-7 (Granulocyte Colony-Stimulating Factor) RN - WYQ7N0BPYC (Acetylcysteine) SB - IM MH - Acetylcysteine/pharmacology MH - Adult MH - Antioxidants/pharmacology MH - Chemokine CCL2/metabolism MH - Exercise/physiology MH - Granulocyte Colony-Stimulating Factor/*metabolism MH - Humans MH - Inflammation/chemically induced/*metabolism MH - Interleukin-6/metabolism MH - Lipopolysaccharides/pharmacology MH - Male MH - Muscle, Skeletal/drug effects/*metabolism MH - Myoblasts/drug effects/metabolism MH - Neutrophils/drug effects/metabolism MH - RNA, Messenger/metabolism MH - Receptors, Granulocyte Colony-Stimulating Factor/*metabolism MH - Tumor Necrosis Factor-alpha/metabolism MH - Young Adult EDAT- 2015/06/10 06:00 MHDA- 2016/06/03 06:00 CRDT- 2015/06/10 06:00 PHST- 2015/06/10 06:00 [entrez] PHST- 2015/06/10 06:00 [pubmed] PHST- 2016/06/03 06:00 [medline] AID - 10.1089/jir.2014.0159 [doi] PST - ppublish SO - J Interferon Cytokine Res. 2015 Sep;35(9):710-9. doi: 10.1089/jir.2014.0159. Epub 2015 Jun 9.