Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

LPS-Induced Modifications in Macrophage Transcript and Secretion Profiles Are Linked to Muscle Wasting and Glucose Intolerance

  • Heeyeon Ryu (Department of Food Science and Nutrition, Pukyong National University) ;
  • Hyeon Hak Jeong (Department of Smart Green Technology Engineering, Pukyong National University) ;
  • Seungjun Lee (Department of Food Science and Nutrition, Pukyong National University) ;
  • Min-Kyeong Lee (Department of Food Science and Nutrition, Pukyong National University) ;
  • Myeong-Jin Kim (Department of Food Science and Nutrition, Pukyong National University) ;
  • Bonggi Lee (Department of Food Science and Nutrition, Pukyong National University)
  • Received : 2023.09.28
  • Accepted : 2023.11.22
  • Published : 2024.02.28
Download PDF
⟨ Previous Next ⟩

Abstract

Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.

Keywords

Acknowledgement

This work was supported by the Korea Institute of Marine Science & Technology Promotion (20220252) and the Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry (821030-3). This work was also supported by the National Research Foundation of Korea (RS-2023-00274576).

References

  1. Gordon S. 1998. The role of the macrophage in immune regulation. Res. Immunol. 149: 685-688.
  2. Chazaud B. 2014. Macrophages: supportive cells for tissue repair and regeneration. Immunobiology 219: 172-178.
  3. Koh TJ, DiPietro LA. 2011. Inflammation and wound healing: the role of the macrophage. Exp. Rev. Mol. Med. 13: e23.
  4. Gordon S, Taylor PR. 2005. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol. 5: 953-964.
  5. McWhorter FY, Wang T, Nguyen P, Chung T, Liu WF. 2013. Modulation of macrophage phenotype by cell shape. Proc. Natl. Acad. Sci. USA 110: 17253-17258.
  6. Wang X, Zhou L. 2022. The many roles of macrophages in skeletal muscle injury and repair. Front. Cell Dev. Biol. 10: 952249.
  7. Tidball JG. 2005. Inflammatory processes in muscle injury and repair. Am. J. Physiol. Regul. Integr. Comp. Physiol. 288: R345-R353.
  8. Yang W, Hu P. 2018. Skeletal muscle regeneration is modulated by inflammation. J. Orthop. Translat. 13: 25-32.
  9. Arnold L, Henry A, Poron F, Baba-Amer Y, Van Rooijen N, Plonquet A, et al. 2007. Inflammatory monocytes recruited after skeletal muscle injury switch into antiinflammatory macrophages to support myogenesis. J. Exp. Med. 204: 1057-1069.
  10. Tidball JG, Villalta SA. 2010. Regulatory interactions between muscle and the immune system during muscle regeneration. Am. J. Physiol. Regul. Integr. Compar. Physiol. 298: R1173-R1187.
  11. Costamagna D, Costelli P, Sampaolesi M, Penna F. 2015. Role of inflammation in muscle homeostasis and myogenesis. Mediators Inflamm. 2015: 805172.
  12. Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, et al. 2004. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 18: 39-51.
  13. Lecker SH, Solomon V, Mitch WE, Goldberg AL. 1999. Muscle protein breakdown and the critical role of the ubiquitin-proteasome pathway in normal and disease states. J. Nutr. 129: 227S-237S.
  14. Jackman RW, Kandarian SC. 2004. The molecular basis of skeletal muscle atrophy. Am. J. Physiol. Cell Physiol. 287: C834-C843.
  15. Merz KE, Thurmond DC. 2011. Role of skeletal muscle in insulin resistance and glucose uptake. Compr. Physiol. 10: 785-809.
  16. Perry BD, Caldow MK, Brennan-Speranza TC, Sbaraglia M, Jerums G, Garnham A, et al. 2016. Muscle atrophy in patients with Type 2 Diabetes Mellitus: roles of inflammatory pathways, physical activity and exercise. Exerc. Immunol. Rev. 22: 94-109.
  17. Li H, Meng Y, He S, Tan X, Zhang Y, Zhang X, et al. 2022. Macrophages, chronic inflammation, and insulin resistance. Cells 11: 3001.
  18. Galicia-Garcia U, Benito-Vicente A, Jebari S, Larrea-Sebal A, Siddiqi H, Uribe KB, et al. 2020. Pathophysiology of type 2 diabetes mellitus. Int. J. Mol. Sci. 21: 6275.
  19. Orecchioni M, Ghosheh Y, Pramod AB, Ley K. 2019. Macrophage polarization: different gene signatures in M1 (LPS+) vs. classically and M2 (LPS-) vs. alternatively activated macrophages. Front. Immunol. 10: 1084.
  20. Fujihara M, Muroi M, Tanamoto K-i, Suzuki T, Azuma H, Ikeda H. 2003. Molecular mechanisms of macrophage activation and deactivation by lipopolysaccharide: roles of the receptor complex. Pharmacol. Ther. 100: 171-194.
  21. Livak KJ, Schmittgen TD. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method. Methods 25: 402-408.
  22. Pertea M, Kim D, Pertea GM, Leek JT, Salzberg SL. 2016. Transcript-level expression analysis of RNA-seq experiments with HISAT, StringTie and Ballgown. Nat. Protoc. 11: 1650-1667.
  23. Kim D, Langmead B, Salzberg SL. 2015. HISAT: a fast spliced aligner with low memory requirements. Nat. Methods 12: 357-360.
  24. Pertea M, Pertea GM, Antonescu CM, Chang T-C, Mendell JT, Salzberg SL. 2015. StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat. Biotechnol. 33: 290-295.
  25. Robinson MD, McCarthy DJ, Smyth GK. 2010. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26: 139-140.
  26. Rom O, Reznick AZ. 2016. The role of E3 ubiquitin-ligases MuRF-1 and MAFbx in loss of skeletal muscle mass. Free Radic. Biol. Med. 98: 218-230.
  27. Kitajima Y, Yoshioka K, Suzuki N. 2020. The ubiquitin-proteasome system in regulation of the skeletal muscle homeostasis and atrophy: from basic science to disorders. J. Physiol. Sci. 70: 40.
  28. Li W, Moylan JS, Chambers MA, Smith J, Reid MB. 2009. Interleukin-1 stimulates catabolism in C2C12 myotubes. Am. J. Physiol. Cell Physiol. 297: C706-C714.
  29. Erekat NS, Al-Jarrah MD. 2018. Interleukin-1 beta and tumor necrosis factor alpha upregulation and nuclear factor kappa B activation in skeletal muscle from a mouse model of chronic/progressive Parkinson disease. Med. Sci. Monit. 24: 7524-7531.
  30. Zhang H, Mulya A, Nieuwoudt S, Vandanmagsar B, McDowell R, Heintz EC, et al. 2023. GDF15 mediates the effect of skeletal muscle contraction on glucose-stimulated insulin secretion. Diabetes 72: 1070-1082.
  31. Haddad F, Zaldivar F, Cooper DM, Adams GR. 2005. IL-6-induced skeletal muscle atrophy. J. Appl. Physiol. 98: 911-917.
  32. Roder PV, Wu B, Liu Y, Han W. 2016. Pancreatic regulation of glucose homeostasis. Exp. Mol. Med. 48: e219-e219.
  33. Grove RI, Allegretto NJ, Kiener PA, Warr GA. 1990. Lipopolysaccharide (LPS) alters phosphatidylcholine metabolism in elicited peritoneal macrophages. J. Leukoc. Biol. 48: 38-42.
  34. Funk JL, Feingold KR, Moser AH, Grunfeld C. 1993. Lipopolysaccharide stimulation of RAW 264.7 macrophages induces lipid accumulation and foam cell formation. Atherosclerosis 98: 67-82.
  35. DU T, Huang H, Chen X, Ding H, Zhang R, Liu M, et al. 2014. LPS regulates macrophage autophagy through PI3 K/Akt/mTOR pathway. Chin. J. Pathophysiol. 675-680.
  36. Kumar L, Bisen M, Khan A, Kumar P, Patel SKS. 2022. Role of matrix metalloproteinases in musculoskeletal diseases. Biomedicines 10: 2477.
  37. Li H, Mittal A, Makonchuk DY, Bhatnagar S, Kumar A. 2009. Matrix metalloproteinase-9 inhibition ameliorates pathogenesis and improves skeletal muscle regeneration in muscular dystrophy. Hum. Mol. Genet. 18: 2584-2598.
  38. Belizario JE, Fontes-Oliveira CC, Borges JP, Kashiabara JA, Vannier E. 2016. Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6. Springerplus 5: 1-15.
  39. Nieto-Vazquez I, Fernandez-Veledo S, de Alvaro C, Lorenzo M. 2008. Dual role of interleukin-6 in regulating insulin sensitivity in murine skeletal muscle. Diabetes 57: 3211-3221.
  40. Shou J, Chen P-J, Xiao W-H. 2020. Mechanism of increased risk of insulin resistance in aging skeletal muscle. Diabetol. Metab. Syndr. 12: 14.
  41. Zhang W, Sun W, Gu X, Miao C, Feng L, Shen Q, et al. 2022. GDF-15 in tumor-derived exosomes promotes muscle atrophy via Bcl-2/caspase-3 pathway. Cell Death Discov. 8: 162.
  42. Eddy AC, Trask AJ. 2021. Growth differentiation factor-15 and its role in diabetes and cardiovascular disease. Cytokine Growth Factor Rev. 57: 11-18.
  43. Han J, Ham JR, Lee MJ, Lee HJ, Son YJ, Lee MK. 2023. "Nulichal" barley extract suppresses nitric oxide and pro-inflammatory cytokine production by lipopolysaccharides in RAW264.7 macrophage cell line. Prev. Nutr. Food Sci. 28: 370-376.
  44. Lim HJ, Han JM, Byun EH. 2022. Evaluation of the immunological activity of Gryllus bimaculatus water extract. Prev. Nutr. Food Sci. 27: 99-107.