Research Article
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Pro-inflammatory ‘M1 macrophage’ vs anti-inflammatory ‘Hydrocortisone’ a new approach to wound healing in HaCaT cells

Year 2023, Volume: 53 Issue: 3, 280 - 286, 28.12.2023
https://doi.org/10.26650/IstanbulJPharm.2023.1229554

Abstract

Background and Aims: Wound healing is a process of repairing the skin that has lost its integrity through inflammation, proliferation, and remodeling. Macrophages exhibit adaptability, transitioning from a pro-inflammatory "M1" to an anti-inflammatory "M2" phenotype throughout wound healing for optimal outcomes. Hydrocortisone’s M2c polarization makes it a key agent for balancing M1/M2 polarization. In this study, we specifically explored the effects of M1 macrophages and hydrocortisone on cell migration and wound healing in HaCaT keratinocytes.

Methods: To better understand how macrophages contribute to wound healing, we created a co-culture scratch assay model of HaCaT cells using M1-polarized macrophages derived from THP-1 cells. In addition, we administered hydrocortisone, ‘an anti-inflammatory drug’, to our experimental groups to compare the effects. We determined the proliferation effects of different concentrations of hydrocortisone and PMA on HaCaT cells. Then, we evaluated the effects of polarized M1 macrophages and hydrocortisone on the wound healing of HaCaT cells by scratch assay and COL1A1 mRNA gene expression levels.

Results: As a result, it was determined that 100 μM hydrocortisone increased HaCaT cell migration and COL1A1 mRNA gene expression compared to control, while M1 polarized macrophages decreased these effects negatively.

Conclusion: To understand the macrophages responsible for the mechanisms of wound healing, much more study is required. Macrophages are a vital component in the healing process for wounds, and the shifting of M1/M2 in the treatment of wounds can potentially lead to the enlargement of novel treatment methods.

References

  • Bashir, S., Sharma, Y., Elahi, A., & Khan, F. (2016). Macrophage polarization: the link between inflammation and related diseases. Inflammation Research, 65(1), 1-11. https://doi.org/10.1007/s00011-015-0874-1 google scholar
  • Basu Mallik, S., Jayashree, B. S., & Shenoy, R. R. (2018). Epige-netic modulation of macrophage polarization- perspectives in di-abetic wounds. Journal of Diabetes and Itscomplications, 32(5), 524-530. https://doi.org/10.1016/j.jdiacomp.2018.01.015 google scholar
  • Calabrese, E. J., Dhawan, G., Kapoor, R., Agathokleous, E., & Calabrese, V. (2022). Hormesis: Wound healing and keratinocytes. Pharmacological Research, 183, 106393. https://doi.org/10.1016/j.phrs.2022.106393 google scholar
  • Chanput, W., Mes, J. J., Savelkoul, H. F., & Wichers, H. J. (2013). Characterization of polarized THP-1 macrophages and polariz-ing ability of LPS and food compounds. Food & Function, 4(2), 266-276. https://doi.org/10.1039/c2fo30156c google scholar
  • Delavary, B. M., van der Veer, W. M., van Egmond, M., Niessen, F. B., & Beelen, R. H. (2011). Macrophages in skin injury and repair. Immunobiology, 216(7), 753-762. https://doi.org/10.1016/j.imbio.2011.01.001 google scholar
  • Engür-Öztürk, S., & Dikmen, M. (2022). Proteasome inhibitor immunotherapy for the epithelial to mesenchymal transition: assessing the A549 lung cancer cell microenvironment and the role of M1, M2a and M2c ’hydrocortisone-polarised’ macrophages. Molecular Biology Reports, 49(6), 4777-4793. https://doi.org/10.1007/s11033-022-07329-w google scholar
  • Foey, A. D. (2014). Immune Response Activation. Guy Huynh Thien Duc (Eds.) Macrophages—masters of immune activation, sup-pression and deviation (pp. 121-149). BoD - Books on Demand Press. google scholar
  • Gelse, K., Pöschl, E., & Aigner, T. (2003). Collagens-structure, func-tion, and biosynthesis. Advanced Drug Delivery Reviews, 55(12), 1531-1546. https://doi.org/10.1016/j.addr.2003.08.002 google scholar
  • Huang, S. M., Wu, C. S., Chiu, M. H., Wu, C. H., Chang, Y. T., Chen, G. S., & Lan, C. E. (2019). High glucose environment induces M1 macrophage polarization that impairs keratinocyte migration via TNF-a: An important mechanism to delay the dia-betic wound healing. Journal of Dermatological Science, 96(3), 159-167. https://doi.org/10.1016/j.jdermsci.2019.11.004 google scholar
  • Huang, X., Li, Y., Fu, M., & Xin, H. B. (2018). Polarizing Macrophages In Vitro. Methods in Molecular Biology, 1784, 119-126. https://doi.org/10.1007/978-1-4939-7837-3_12 google scholar
  • Kim, S. Y., & Nair, M. G. (2019). Macrophages in wound healing: activation and plasticity. Immunology and Cell Biology, 97(3), 258-267. https://doi.org/10.1111/imcb.12236 google scholar
  • Koh, T. J., & DiPietro, L. A. (2011). Inflammation and wound healing: the role of the macrophage. Expert reviews in Molecular Medicine, 13, e23. https://doi.org/10.1017/S1462399411001943 google scholar
  • Kongkadee, K., Wisuitiprot, W., Ingkaninan, K., & Waranuch, N. (2022). Anti-inflammation and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabid-iol: An in vitro study. Archives of Oral Biology, 140, 105464. https://doi.org/10.1016/j.archoralbio.2022.105464 google scholar
  • Krieg, T., & Aumailley, M. (2011). The extracellular matrix of the dermis: flexible structures with dynamic functions. Experimen-tal Dermatology, 20(8), 689-695. https://doi.org/10.1111/j.1600-0625.2011.01313.x google scholar
  • Leibovich, S. J., & Ross, R. (1975). The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. The American Journal of Pathology, 78(1), 71. google scholar
  • Loots, M. A., Lamme, E. N., Zeegelaar, J., Mekkes, J. R., Bos, J. D., & Middelkoop, E. (1998). Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. Journal of Investigative Dermatology, 111(5), 850857. google scholar
  • Louiselle, A. E., Niemiec, S. M., Zgheib, C., & Liechty, K. W. (2021). Macrophage polarization and diabetic wound healing. Translational Research: The Journal of Laboratory and Clinical Medicine, 236, 109-116.j.trsl.2021.05.006 google scholar
  • Miao, M., Niu, Y., Xie, T., Yuan, B., Qing, C., & Lu, S. (2012). Diabetes-impaired wound healing and altered macrophage ac-tivation: a possible pathophysiologic correlation. Wound repair and regeneration: official publication of the Wound Healing So-ciety [and] the European Tissue Repair Society, 20(2), 203-213. https://doi.org/10.1111/j.1524-475X.2012.00772.x google scholar
  • Orecchioni, M., Ghosheh, Y., Pramod, A. B., & Ley, K. (2019). Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Frontiers in Immunology, 10, 1084. https://doi.org/10.3389/fimmu.2019.01084 google scholar
  • Öztürk, A. A., Çevikelli, T., Tilki, E. K., Güven, U. M., & Kıyan, H. T. (2023). Ketorolac Tromethamine Loaded Nano-Spray Dried Nanoparticles: Preparation, Characteriza-tion, Cell Viability, COL1A1 Gene Simulation and Deter-mination of Anti-inflammatory Activity by In vivo HET-CAM Assay. Current Drug Delivery, 20(6), 830-840. https://doi.org/10.2174/1567201820666230125144133 google scholar
  • Rahmannia, M., Amini, A., Chien, S., & Bayat, M. (2022). Impact of photobiomodulation on macrophages and their polarization during diabetic wound healing: a systematic review. Lasers in Medical Science, 37(7), 2805-2815. https://doi.org/10.1007/s10103-022-03581-5 google scholar
  • Shapouri-Moghaddam, A., Mohammadian, S., Vazini, H., Tagha-dosi, M., Esmaeili, S. A., Mardani, F., Seifi, B., Moham-madi, A., Afshari, J. T., & Sahebkar, A. (2018). Macrophage plasticity, polarization, and function in health and dis-ease. Journal of Cellular Physiology, 233(9), 6425-6440. https://doi.org/10.1002/jcp.26429 google scholar
  • Sharifiaghdam, M., Shaabani, E., Faridi-Majidi, R., De Smedt, S. C., Braeckmans, K., & Fraire, J. C. (2022). Macrophages as a therapeutic target to promote diabetic wound healing. Molecular therapy: the journal of the American Society of Gene Therapy, 30(9), 2891-2908. https://doi.org/10.1016/j.ymthe.2022.07.016 google scholar
  • Terao, M., & Katayama, I. (2016). Local cortisol/corticosterone activation in skin physiology and pathology. Jour-nal of Dermatological Science, 84(1), 11-16.https://doi.org/10.1016/j.jdermsci.2016.06.014 google scholar
  • Tu, G. W., Shi, Y., Zheng, Y. J., Ju, M. J., He, H. Y., Ma, G. G., Hao, G. W., & Luo, Z. (2017). Glucocorticoid attenuates acute lung injury through induction of type 2 macrophage. Journal of Translational Medicine , 15(1), 181. https://doi.org/10.1186/s12967-017-1284-7 google scholar
  • Wu, M. H., Shih, M. H., Hsu, W. B., Dubey, N. K., Lee, W. F., Lin, T. Y., Hsieh, M. Y., Chen, C. F., Peng, K. T., Huang, T. J., Shi, C. S., Guo, R. S., Cai, C. J., Chung, C. Y., & Wong, C. H. (2017). Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model. PloS one,12(10), e0186784. https://doi.org/10.1371/journal.pone.0186784 google scholar
  • Yuksel, S. N., Dikmen, M., & Canturk, Z. (2021). Evaluation of Real Time Cell Proliferation, Anti-Inflammatory and Wound Heal-ing Potential of Helenalin on HaCaT Keratinocytes Treated with Lipopolysaccharide Stimulated Monocytes. Indian Journal of Pharmaceutical Sciences, 83(2), 219-229. google scholar
Year 2023, Volume: 53 Issue: 3, 280 - 286, 28.12.2023
https://doi.org/10.26650/IstanbulJPharm.2023.1229554

Abstract

References

  • Bashir, S., Sharma, Y., Elahi, A., & Khan, F. (2016). Macrophage polarization: the link between inflammation and related diseases. Inflammation Research, 65(1), 1-11. https://doi.org/10.1007/s00011-015-0874-1 google scholar
  • Basu Mallik, S., Jayashree, B. S., & Shenoy, R. R. (2018). Epige-netic modulation of macrophage polarization- perspectives in di-abetic wounds. Journal of Diabetes and Itscomplications, 32(5), 524-530. https://doi.org/10.1016/j.jdiacomp.2018.01.015 google scholar
  • Calabrese, E. J., Dhawan, G., Kapoor, R., Agathokleous, E., & Calabrese, V. (2022). Hormesis: Wound healing and keratinocytes. Pharmacological Research, 183, 106393. https://doi.org/10.1016/j.phrs.2022.106393 google scholar
  • Chanput, W., Mes, J. J., Savelkoul, H. F., & Wichers, H. J. (2013). Characterization of polarized THP-1 macrophages and polariz-ing ability of LPS and food compounds. Food & Function, 4(2), 266-276. https://doi.org/10.1039/c2fo30156c google scholar
  • Delavary, B. M., van der Veer, W. M., van Egmond, M., Niessen, F. B., & Beelen, R. H. (2011). Macrophages in skin injury and repair. Immunobiology, 216(7), 753-762. https://doi.org/10.1016/j.imbio.2011.01.001 google scholar
  • Engür-Öztürk, S., & Dikmen, M. (2022). Proteasome inhibitor immunotherapy for the epithelial to mesenchymal transition: assessing the A549 lung cancer cell microenvironment and the role of M1, M2a and M2c ’hydrocortisone-polarised’ macrophages. Molecular Biology Reports, 49(6), 4777-4793. https://doi.org/10.1007/s11033-022-07329-w google scholar
  • Foey, A. D. (2014). Immune Response Activation. Guy Huynh Thien Duc (Eds.) Macrophages—masters of immune activation, sup-pression and deviation (pp. 121-149). BoD - Books on Demand Press. google scholar
  • Gelse, K., Pöschl, E., & Aigner, T. (2003). Collagens-structure, func-tion, and biosynthesis. Advanced Drug Delivery Reviews, 55(12), 1531-1546. https://doi.org/10.1016/j.addr.2003.08.002 google scholar
  • Huang, S. M., Wu, C. S., Chiu, M. H., Wu, C. H., Chang, Y. T., Chen, G. S., & Lan, C. E. (2019). High glucose environment induces M1 macrophage polarization that impairs keratinocyte migration via TNF-a: An important mechanism to delay the dia-betic wound healing. Journal of Dermatological Science, 96(3), 159-167. https://doi.org/10.1016/j.jdermsci.2019.11.004 google scholar
  • Huang, X., Li, Y., Fu, M., & Xin, H. B. (2018). Polarizing Macrophages In Vitro. Methods in Molecular Biology, 1784, 119-126. https://doi.org/10.1007/978-1-4939-7837-3_12 google scholar
  • Kim, S. Y., & Nair, M. G. (2019). Macrophages in wound healing: activation and plasticity. Immunology and Cell Biology, 97(3), 258-267. https://doi.org/10.1111/imcb.12236 google scholar
  • Koh, T. J., & DiPietro, L. A. (2011). Inflammation and wound healing: the role of the macrophage. Expert reviews in Molecular Medicine, 13, e23. https://doi.org/10.1017/S1462399411001943 google scholar
  • Kongkadee, K., Wisuitiprot, W., Ingkaninan, K., & Waranuch, N. (2022). Anti-inflammation and gingival wound healing activities of Cannabis sativa L. subsp. sativa (hemp) extract and cannabid-iol: An in vitro study. Archives of Oral Biology, 140, 105464. https://doi.org/10.1016/j.archoralbio.2022.105464 google scholar
  • Krieg, T., & Aumailley, M. (2011). The extracellular matrix of the dermis: flexible structures with dynamic functions. Experimen-tal Dermatology, 20(8), 689-695. https://doi.org/10.1111/j.1600-0625.2011.01313.x google scholar
  • Leibovich, S. J., & Ross, R. (1975). The role of the macrophage in wound repair. A study with hydrocortisone and antimacrophage serum. The American Journal of Pathology, 78(1), 71. google scholar
  • Loots, M. A., Lamme, E. N., Zeegelaar, J., Mekkes, J. R., Bos, J. D., & Middelkoop, E. (1998). Differences in cellular infiltrate and extracellular matrix of chronic diabetic and venous ulcers versus acute wounds. Journal of Investigative Dermatology, 111(5), 850857. google scholar
  • Louiselle, A. E., Niemiec, S. M., Zgheib, C., & Liechty, K. W. (2021). Macrophage polarization and diabetic wound healing. Translational Research: The Journal of Laboratory and Clinical Medicine, 236, 109-116.j.trsl.2021.05.006 google scholar
  • Miao, M., Niu, Y., Xie, T., Yuan, B., Qing, C., & Lu, S. (2012). Diabetes-impaired wound healing and altered macrophage ac-tivation: a possible pathophysiologic correlation. Wound repair and regeneration: official publication of the Wound Healing So-ciety [and] the European Tissue Repair Society, 20(2), 203-213. https://doi.org/10.1111/j.1524-475X.2012.00772.x google scholar
  • Orecchioni, M., Ghosheh, Y., Pramod, A. B., & Ley, K. (2019). Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS-) vs. Alternatively Activated Macrophages. Frontiers in Immunology, 10, 1084. https://doi.org/10.3389/fimmu.2019.01084 google scholar
  • Öztürk, A. A., Çevikelli, T., Tilki, E. K., Güven, U. M., & Kıyan, H. T. (2023). Ketorolac Tromethamine Loaded Nano-Spray Dried Nanoparticles: Preparation, Characteriza-tion, Cell Viability, COL1A1 Gene Simulation and Deter-mination of Anti-inflammatory Activity by In vivo HET-CAM Assay. Current Drug Delivery, 20(6), 830-840. https://doi.org/10.2174/1567201820666230125144133 google scholar
  • Rahmannia, M., Amini, A., Chien, S., & Bayat, M. (2022). Impact of photobiomodulation on macrophages and their polarization during diabetic wound healing: a systematic review. Lasers in Medical Science, 37(7), 2805-2815. https://doi.org/10.1007/s10103-022-03581-5 google scholar
  • Shapouri-Moghaddam, A., Mohammadian, S., Vazini, H., Tagha-dosi, M., Esmaeili, S. A., Mardani, F., Seifi, B., Moham-madi, A., Afshari, J. T., & Sahebkar, A. (2018). Macrophage plasticity, polarization, and function in health and dis-ease. Journal of Cellular Physiology, 233(9), 6425-6440. https://doi.org/10.1002/jcp.26429 google scholar
  • Sharifiaghdam, M., Shaabani, E., Faridi-Majidi, R., De Smedt, S. C., Braeckmans, K., & Fraire, J. C. (2022). Macrophages as a therapeutic target to promote diabetic wound healing. Molecular therapy: the journal of the American Society of Gene Therapy, 30(9), 2891-2908. https://doi.org/10.1016/j.ymthe.2022.07.016 google scholar
  • Terao, M., & Katayama, I. (2016). Local cortisol/corticosterone activation in skin physiology and pathology. Jour-nal of Dermatological Science, 84(1), 11-16.https://doi.org/10.1016/j.jdermsci.2016.06.014 google scholar
  • Tu, G. W., Shi, Y., Zheng, Y. J., Ju, M. J., He, H. Y., Ma, G. G., Hao, G. W., & Luo, Z. (2017). Glucocorticoid attenuates acute lung injury through induction of type 2 macrophage. Journal of Translational Medicine , 15(1), 181. https://doi.org/10.1186/s12967-017-1284-7 google scholar
  • Wu, M. H., Shih, M. H., Hsu, W. B., Dubey, N. K., Lee, W. F., Lin, T. Y., Hsieh, M. Y., Chen, C. F., Peng, K. T., Huang, T. J., Shi, C. S., Guo, R. S., Cai, C. J., Chung, C. Y., & Wong, C. H. (2017). Evaluation of a novel biodegradable thermosensitive keto-hydrogel for improving postoperative pain in a rat model. PloS one,12(10), e0186784. https://doi.org/10.1371/journal.pone.0186784 google scholar
  • Yuksel, S. N., Dikmen, M., & Canturk, Z. (2021). Evaluation of Real Time Cell Proliferation, Anti-Inflammatory and Wound Heal-ing Potential of Helenalin on HaCaT Keratinocytes Treated with Lipopolysaccharide Stimulated Monocytes. Indian Journal of Pharmaceutical Sciences, 83(2), 219-229. google scholar
There are 27 citations in total.

Details

Primary Language English
Subjects Pharmacology and Pharmaceutical Sciences
Journal Section Original Article
Authors

Selin Engür Öztürk 0000-0003-1534-8117

Publication Date December 28, 2023
Submission Date January 4, 2023
Published in Issue Year 2023 Volume: 53 Issue: 3

Cite

APA Engür Öztürk, S. (2023). Pro-inflammatory ‘M1 macrophage’ vs anti-inflammatory ‘Hydrocortisone’ a new approach to wound healing in HaCaT cells. İstanbul Journal of Pharmacy, 53(3), 280-286. https://doi.org/10.26650/IstanbulJPharm.2023.1229554
AMA Engür Öztürk S. Pro-inflammatory ‘M1 macrophage’ vs anti-inflammatory ‘Hydrocortisone’ a new approach to wound healing in HaCaT cells. iujp. December 2023;53(3):280-286. doi:10.26650/IstanbulJPharm.2023.1229554
Chicago Engür Öztürk, Selin. “Pro-Inflammatory ‘M1 macrophage’ Vs Anti-Inflammatory ‘Hydrocortisone’ a New Approach to Wound Healing in HaCaT Cells”. İstanbul Journal of Pharmacy 53, no. 3 (December 2023): 280-86. https://doi.org/10.26650/IstanbulJPharm.2023.1229554.
EndNote Engür Öztürk S (December 1, 2023) Pro-inflammatory ‘M1 macrophage’ vs anti-inflammatory ‘Hydrocortisone’ a new approach to wound healing in HaCaT cells. İstanbul Journal of Pharmacy 53 3 280–286.
IEEE S. Engür Öztürk, “Pro-inflammatory ‘M1 macrophage’ vs anti-inflammatory ‘Hydrocortisone’ a new approach to wound healing in HaCaT cells”, iujp, vol. 53, no. 3, pp. 280–286, 2023, doi: 10.26650/IstanbulJPharm.2023.1229554.
ISNAD Engür Öztürk, Selin. “Pro-Inflammatory ‘M1 macrophage’ Vs Anti-Inflammatory ‘Hydrocortisone’ a New Approach to Wound Healing in HaCaT Cells”. İstanbul Journal of Pharmacy 53/3 (December 2023), 280-286. https://doi.org/10.26650/IstanbulJPharm.2023.1229554.
JAMA Engür Öztürk S. Pro-inflammatory ‘M1 macrophage’ vs anti-inflammatory ‘Hydrocortisone’ a new approach to wound healing in HaCaT cells. iujp. 2023;53:280–286.
MLA Engür Öztürk, Selin. “Pro-Inflammatory ‘M1 macrophage’ Vs Anti-Inflammatory ‘Hydrocortisone’ a New Approach to Wound Healing in HaCaT Cells”. İstanbul Journal of Pharmacy, vol. 53, no. 3, 2023, pp. 280-6, doi:10.26650/IstanbulJPharm.2023.1229554.
Vancouver Engür Öztürk S. Pro-inflammatory ‘M1 macrophage’ vs anti-inflammatory ‘Hydrocortisone’ a new approach to wound healing in HaCaT cells. iujp. 2023;53(3):280-6.