IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Recombinant Human IL-32θ Induces Polarization Into M1-like Macrophage in Human Monocytic Cells

  • Hyo-Min Park (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Jae-Young Park (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Na-Yeon Kim (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Hyemoon Kim (Boson Bioscience) ;
  • Hong-Gyum Kim (Boson Bioscience) ;
  • Dong-Ju Son (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Jin Tae Hong (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Do-Young Yoon (Department of Bioscience and Biotechnology, Konkuk University)
  • Received : 2023.12.22
  • Accepted : 2024.04.29
  • Published : 2024.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

The tumor microenvironment (TME) is formed by several immune cells. Notably, tumor-associated macrophages (TAMs) are existed in the TME that induce angiogenesis, metastasis, and proliferation of cancer cells. Recently, a point-mutated variant of IL-32θ was discovered in breast cancer tissues, which suppressed migration and proliferation through intracellular pathways. Although the relationship between cancer and IL-32 has been previously studied, the effects of IL-32θ on TAMs remain elusive. Recombinant human IL-32θ (rhIL-32θ) was generated using an Escherichia coli expression system. To induce M0 macrophage polarization, THP-1 cells were stimulated with PMA. After PMA treatment, the cells were cultured with IL-4 and IL-13, or rhIL-32θ. The mRNA level of M1 macrophage markers (IL-1β, TNFα, inducible nitric oxide synthase) were increased by rhIL-32θ in M0 macrophages. On the other hand, the M2 macrophage markers (CCL17, CCL22, TGFβ, CD206) were decreased by rhIL-32θ in M2 macrophages. rhIL-32θ induced nuclear translocation of the NF-κB via regulation of the MAPK (p38) pathway. In conclusion, point-mutated rhIL-32θ induced the polarization to M1-like macrophages through the MAPK (p38) and NF-κB (p65/p50) pathways.

Keywords

Acknowledgement

We would like to thank Editage (www.editage.co.kr) for their assistance with English language editing (No. KOUNI-5228).

References

  1. Bray F, Laversanne M, Weiderpass E, Soerjomataram I. The ever-increasing importance of cancer as a leading cause of premature death worldwide. Cancer 2021;127:3029-3030.
  2. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023;73:17-48.
  3. Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther 2021;221:107753.
  4. Chen Y, Song Y, Du W, Gong L, Chang H, Zou Z. Tumor-associated macrophages: an accomplice in solid tumor progression. J Biomed Sci 2019;26:78.
  5. Liu C, Chikina M, Deshpande R, Menk AV, Wang T, Tabib T, Brunazzi EA, Vignali KM, Sun M, Stolz DB, et al. Treg cells promote the SREBP1-dependent metabolic fitness of tumor-promoting macrophages via repression of CD8+ T cell-derived interferon-γ. Immunity 2019;51:381-397.e6.
  6. Denning TL, Wang YC, Patel SR, Williams IR, Pulendran B. Lamina propria macrophages and dendritic cells differentially induce regulatory and interleukin 17-producing T cell responses. Nat Immunol 2007;8:1086-1094.
  7. Strachan DC, Ruffell B, Oei Y, Bissell MJ, Coussens LM, Pryer N, Daniel D. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. OncoImmunology 2013;2:e26968.
  8. Kim SH, Han SY, Azam T, Yoon DY, Dinarello CA. Interleukin-32: a cytokine and inducer of TNFα. Immunity 2005;22:131-142.
  9. Goda C, Kanaji T, Kanaji S, Tanaka G, Arima K, Ohno S, Izuhara K. Involvement of IL-32 in activation-induced cell death in T cells. Int Immunol 2006;18:233-240.
  10. Kang JW, Park YS, Lee DH, Kim MS, Bak Y, Ham SY, Park SH, Kim H, Ahn JH, Hong JT, et al. Interaction network mapping among IL-32 isoforms. Biochimie 2014;101:248-251.
  11. Aass KR, Kastnes MH, Standal T. Molecular interactions and functions of IL-32. J Leukoc Biol 2021;109:143-159.
  12. Sohn DH, Nguyen TT, Kim S, Shim S, Lee S, Lee Y, Jhun H, Azam T, Kim J, Kim S. Structural characteristics of seven IL-32 variants. Immune Netw 2019;19:e8.
  13. Hong JT, Son DJ, Lee CK, Yoon DY, Lee DH, Park MH. Interleukin 32, inflammation and cancer. Pharmacol Ther 2017;174:127-137.
  14. Pham TH, Bak Y, Kwon T, Kwon SB, Oh JW, Park JH, Choi YK, Hong JT, Yoon DY. Interleukin-32θ inhibits tumor-promoting effects of macrophage-secreted CCL18 in breast cancer. Cell Commun Signal 2019;17:53.
  15. Bak Y, Kang JW, Kim MS, Park YS, Kwon T, Kim S, Hong J, Yoon DY. IL-32θ downregulates CCL5 expression through its interaction with PKCδ and STAT3. Cell Signal 2014;26:3007-3015.
  16. Kim MS, Kang JW, Lee DH, Bak Y, Park YS, Song YS, Ham SY, Oh DK, Hong J, Yoon DY. IL-32θ negatively regulates IL-1β production through its interaction with PKCδ and the inhibition of PU.1 phosphorylation. FEBS Lett 2014;588:2822-2829.
  17. Bak Y, Kwon T, Bak IS, Hong J, Yu DY, Yoon DY. IL-32θ inhibits stemness and epithelial-mesenchymal transition of cancer stem cells via the STAT3 pathway in colon cancer. Oncotarget 2016;7:7307-7317.
  18. Park HM, Park JY, Kim NY, Kim J, Pham TH, Hong JT, Yoon DY. Modulatory effects of point-mutated IL-32θ (A94V) on tumor progression in triple-negative breast cancer cells. Biofactors 2024;50:294-310.
  19. Park JY, Park HM, Kim S, Jeon KB, Lim CM, Hong JT, Yoon DY. Human IL-32θA94V mutant attenuates monocyte-endothelial adhesion by suppressing the expression of ICAM-1 and VCAM-1 via binding to cell surface receptor integrin αVβ3 and αVβ6 in TNF-α-stimulated HUVECs. Front Immunol 2023;14:1160301.
  20. Kim KH, Shim JH, Seo EH, Cho MC, Kang JW, Kim SH, Yu DY, Song EY, Lee HG, Sohn JH, et al. Interleukin-32 monoclonal antibodies for immunohistochemistry, western blotting, and ELISA. J Immunol Methods 2008;333:38-50.
  21. Rhee I. Diverse macrophages polarization in tumor microenvironment. Arch Pharm Res 2016;39:1588-1596.
  22. Shettigar A, Salunke R, Modi D, Mukherjee N. Targeting molecular cross-talk between tumor cells and tumor associated macrophage as therapeutic strategy in triple negative breast cancer. Int Immunopharmacol 2023;119:110250.
  23. Pan Y, Yu Y, Wang X, Zhang T. Tumor-associated macrophages in tumor immunity. Front Immunol 2020;11:583084.
  24. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F, Seifi B, Mohammadi A, Afshari JT, Sahebkar A. Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 2018;233:6425-6440.
  25. Atri C, Guerfali FZ, Laouini D. Role of human macrophage polarization in inflammation during infectious diseases. Int J Mol Sci 2018;19:1801.
  26. Pantschenko AG, Pushkar I, Anderson KH, Wang Y, Miller LJ, Kurtzman SH, Barrows G, Kreutzer DL. The interleukin-1 family of cytokines and receptors in human breast cancer: implications for tumor progression. Int J Oncol 2003;23:269-284.
  27. Zelova H, Hosek J. TNF-α signalling and inflammation: interactions between old acquaintances. Inflamm Res 2013;62:641-651.
  28. Yao Y, Xu XH, Jin L. Macrophage polarization in physiological and pathological pregnancy. Front Immunol 2019;10:792.
  29. Heinrich F, Lehmbecker A, Raddatz BB, Kegler K, Tipold A, Stein VM, Kalkuhl A, Deschl U, Baumgartner W, Ulrich R, et al. Morphologic, phenotypic, and transcriptomic characterization of classically and alternatively activated canine blood-derived macrophages in vitro. PLoS One 2017;12:e0183572.
  30. Qin S, Yang C, Huang W, Du S, Mai H, Xiao J, Lu T. Sulforaphane attenuates microglia-mediated neuronal necroptosis through down-regulation of MAPK/NF-κB signaling pathways in LPS-activated BV-2 microglia. Pharmacol Res 2018;133:218-235.
  31. Koh YC, Yang G, Lai CS, Weerawatanakorn M, Pan MH. Chemopreventive effects of phytochemicals and medicines on M1/M2 polarized macrophage role in inflammation-related diseases. Int J Mol Sci 2018;19:2208.
  32. Margraf A, Perretti M. Immune cell plasticity in inflammation: insights into description and regulation of immune cell phenotypes. Cells 2022;11:1824.
  33. Khan SU, Khan MU, Azhar Ud Din M, Khan IM, Khan MI, Bungau S, Hassan SS. Reprogramming tumor-associated macrophages as a unique approach to target tumor immunotherapy. Front Immunol 2023;14:1166487.
  34. Boutilier AJ, Elsawa SF. Macrophage polarization states in the tumor microenvironment. Int J Mol Sci 2021;22:6995.
  35. Yunna C, Mengru H, Lei W, Weidong C. Macrophage M1/M2 polarization. Eur J Pharmacol 2020;877:173090.
  36. Gensel JC, Zhang B. Macrophage activation and its role in repair and pathology after spinal cord injury. Brain Res 2015;1619:1-11.
  37. Najafi M, Hashemi Goradel N, Farhood B, Salehi E, Nashtaei MS, Khanlarkhani N, Khezri Z, Majidpoor J, Abouzaripour M, Habibi M, et al. Macrophage polarity in cancer: a review. J Cell Biochem 2019;120:2756-2765.
  38. Wang H, Yung MM, Ngan HY, Chan KK, Chan DW. The impact of the tumor microenvironment on macrophage polarization in cancer metastatic progression. Int J Mol Sci 2021;22:6560.
  39. Amer HT, Stein U, El Tayebi HM. The monocyte, a maestro in the tumor microenvironment (TME) of breast cancer. Cancers (Basel) 2022;14:5460.
  40. Liu J, Geng X, Hou J, Wu G. New insights into M1/M2 macrophages: key modulators in cancer progression. Cancer Cell Int 2021;21:389.
  41. Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol 2017;14:399-416.
  42. Debela DT, Muzazu SG, Heraro KD, Ndalama MT, Mesele BW, Haile DC, Kitui SK, Manyazewal T. New approaches and procedures for cancer treatment: current perspectives. SAGE Open Med 2021;9:20503121211034366.
  43. Shin MH, Oh E, Kim Y, Nam DH, Jeon SY, Yu JH, Minn D. Recent advances in car-based solid tumor immunotherapy. Cells 2023;12:1606.
  44. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J 2021;11:69.