The DOI matches its Crossref record; 67 of the 68 references it cites were found in a registry or an index.
IL-10 Triggers Changes in Macrophage Phenotype That Promote Muscle Growth and Regeneration
Open accessAbstract
We examined the function of IL-10 in regulating changes in macrophage phenotype during muscle growth and regeneration following injury. Our findings showed that the Th1 cytokine response in inflamed muscle is characterized by high levels of expression of CD68, CCL-2, TNF-α, and IL-6 at 1 d postinjury. During transition to the Th2 cytokine response, expression of those transcripts declined, whereas CD163, IL-10, IL-10R1, and arginase-1 increased. Ablation of IL-10 amplified the Th1 response at 1 d postinjury, causing increases in IL-6 and CCL2, while preventing a subsequent increase in CD163 and arginase-1. Reductions in muscle fiber damage that normally occurred between 1 and 4 d postinjury did not occur in IL-10 mutants. In addition, muscle regeneration and growth were greatly slowed by loss of IL-10. Furthermore, myogenin expression increased in IL-10 mutant muscle at 1 d postinjury, suggesting that the mutation amplified the transition from the proliferative to the early differentiation stages of myogenesis. In vitro assays showed that stimulation of muscle cells with IL-10 had no effect on cell proliferation or expression of MyoD or myogenin. However, coculturing muscle cells with macrophages activated with IL-10 to the M2 phenotype increased myoblast proliferation without affecting MyoD or myogenin expression, showing that M2 macrophages promote the early, proliferative stage of myogenesis. Collectively, these data show that IL-10 plays a central role in regulating the switch of muscle macrophages from a M1 to M2 phenotype in injured muscle in vivo, and this transition is necessary for normal growth and regeneration of muscle.
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“In mouse skeletal muscle injury by chemical toxin or unloading/reloading, IL-4 mRNA, although detectable, does not rise above uninjured levels over the course of healing [73,74].”
From Macrophage phenotypes during tissue repair (2013) · cites this paper as [73]
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Cites
The chemokine system in diverse forms of macrophage activation and polarization
MANTOVANI, A., SICA, A., SOZZANI, S., ALLAVENA, P., VECCHI, A., & LOCATI, M. (2004) · Trends in Immunology · doi:10.1016/j.it.2004.09.015 · Cited by 6,534 · cited 1×
“4), all of which are cytokines that typify a Th1 cytokine response (27).”
BackgroundFadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., & Henson, P. M. (1998) · Journal of Clinical Investigation · doi:10.1172/jci1112 · Cited by 3,166 · cited 2×
“Furthermore, phagocytosis of apoptotic neutrophils by M1 macrophages increased production of the Th2 cytokine TGF-b by the macrophages, while reducing expression of the Th1 cytokines IL-1b and TNF-a, reflecting a shift toward an M2 phenotype (52).”
BackgroundCellular and Molecular Regulation of Muscle Regeneration
CHARGÉ, S. B. P., & Rudnicki, M. A. (2004) · Physiological Reviews · doi:10.1152/physrev.00019.2003 · Cited by 2,691 · cited 1×
“The transition during myogenesis to a stage at which myogenin expression is elevated is developmentally important, because it represents the transition from a proliferative population of myogenic cells that is unable to undergo terminal differentiation to a population that has permanently withdrawn from the cell cycle…”
BackgroundArnold, L., Henry, A., Poron, F., Baba-Amer, Y., van Rooijen, N., Plonquet, A., Gherardi, R. K., & Chazaud, B. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070075 · Cited by 2,002 · cited 3×
“These findings contrast with a previous report that showed that cocultures of muscle cells with macrophages that had been activated with the corticosteroid dexamethasone together with IL-10 caused no change in myoblast proliferation, but they increased myogenin expression (18).”
BackgroundResultInfluentialRegulatory interactions between muscle and the immune system during muscle regeneration
Tidball, J. G., & Villalta, S. A. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00735.2009 · Cited by 1,105 · cited 1×
“C hanges in muscle use or acute damage produce a rapid and highly structured inflammatory response that is dominated by successive waves of invasion of myeloid cells that can strongly influence both the magnitude of muscle damage and the rate at which repair occurs (1).”
BackgroundSelf-citationHeme oxygenase-1 mediates the anti-inflammatory effect of interleukin-10 in mice
Lee, T.-S., & Chau, L.-Y. (2002) · Nature Medicine · doi:10.1038/nm0302-240 · Cited by 1,019 · cited 5×
“However, expression of heme oxygenase-1 (HMOX-1), which can be activated by CD163 ligation (37), was not increased at 4 d (Fig.”
BackgroundInfluentialHindlimb unloading rodent model: technical aspects
Morey, E. R., & Globus, R. K. (2002) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00969.2001 · Cited by 998
Cornelison, D., & Wold, B. J. (1997) · Developmental Biology · doi:10.1006/dbio.1997.8721 · Cited by 934 · cited 1×
“withdraw from the cell cycle, and the expression of myogenin, also a transcription factor, increases (20, 21).”
BackgroundInterleukin-6 Is an Essential Regulator of Satellite Cell-Mediated Skeletal Muscle Hypertrophy
Serrano, A. L., Baeza-Raja, B., Perdiguero, E., Jardí, M., & Muñoz-Cánoves, P. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.011 · Cited by 873 · cited 1×
“However, the relationships between IL-6 and myoblast proliferation and differentiation are complex; IL-6 is well established as a muscle mitogen (25) that plays a significant role in muscle fiber growth (42), but it can also induce muscle wasting (43).”
BackgroundAtrophy of the soleus muscle by hindlimb unweighting
Thomason, D. B., & Booth, F. W. (1990) · Journal of Applied Physiology · doi:10.1152/jappl.1990.68.1.1 · Cited by 631 · cited 1×
“The soleus muscle is most rapidly affected and can lose 30 to 40% of its mass in 10 d through mechanisms that resemble those that occur in the muscles of patients subjected to prolonged bedrest (34).”
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Cited by
Sorted by citations
Macrophages in Tissue Repair, Regeneration, and Fibrosis
Wynn, T. A., & Vannella, K. M. (2016) · Immunity · doi:10.1016/j.immuni.2016.02.015 · Cited by 4,481
Microglial M1/M2 polarization and metabolic states
Orihuela, R., McPherson, C. A., & Harry, G. J. (2016) · British Journal of Pharmacology · doi:10.1111/bph.13139 · Cited by 2,070
“While the initial response of macrophages to injury has been known for some time, positive influences on tissue remodelling have been recognized more recently (Longbrake et al., 2007; Ruffell et al., 2009; Deng et al., 2012; Novak and Koh, 2013; Shechter and Schwartz, 2013; Shechter et al., 2013).”
BackgroundMuscle damage and inflammation during recovery from exercise.
Peake, J., Neubauer, O., Gatta, P. D. D., & Nosaka, K. (2016) · Journal of applied physiology · doi:10.1152/japplphysiol.00971.2016 · Cited by 740
“apoptosis and stimulate their proliferation, promote muscle regeneration and growth, as 373 well as the production of connective tissue (13, 23, 104).”
BackgroundInfluentialRegulation of Muscle Growth and Regeneration by the Immune System
Tidball, J. G. (2017) · Nature Reviews Immunology · doi:10.1038/nri.2016.150 · Cited by 740
Self-citationMacrophages in inflammation, repair and regeneration
Oishi, Y., & Manabe, I. (2018) · International Immunology · doi:10.1093/intimm/dxy054 · Cited by 770
Metadata
- Authors
- Deng, B., Wehling-Henricks, M., Villalta, S. A., Wang, Y., & Tidball, J. G.
- Affiliations
- University of California, Los Angeles (US)
- Department of Integrative Biology and Physiology, University of California , Los Angeles, Los Angeles, CA 90095
- Corresponding author
- Deng, Bo
- Wang, Ying
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-10-01
- Volume
- 189
- Issue
- 7
- Pages
- 3669-3680
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3448810
- OpenAlex
- W2153554828
- Cited by
- 472
- References
- 68
- Citations by year
- 2026: 24 · 2025: 25 · 2024: 26 · 2023: 33 · 2022: 43 · 2021: 40 · 2020: 41 · 2019: 44 · 2018: 32 · 2017: 43 · 2016: 43 · 2015: 28 · 2014: 27 · 2013: 22 · 2012: 1
- FWCI
- 9.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Muscular Dystrophy Association (157881)
- National Institutes of Health (R01 AR/AG054451)
- National Institute on Aging (R01 AR/AG054451)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR047855, R01AR054451, R01AR047721)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Keywords
- IL-10, muscle regeneration, muscle growth, macrophage polarization, M2 macrophages, M1 macrophages, Th1/Th2 shift, muscle damage, myogenesis, myoblast proliferation, arginase-1, CD163, myogenin, MyoD, MCP-1, TNF-α, interleukin-6
- MeSH terms
- Animals, Female, Macrophages, Mice, Inbred C57BL, Regeneration, Up-Regulation, Immunophenotyping, Cytokines, Interleukin-10, Mice, Knockout, Th1 Cells, Th2 Cells, Muscle, Skeletal, Cell Enlargement, Cell Proliferation, Mice, Mice, 129 Strain
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