The Effect of NLRP3 Inflammasome on Wound Healing

Authors

  • Nur Aliviya Ananda Student of the Medical Profession Program, Faculty of Medicine, Muslim University of Indonesia
  • Reeny Purnamasari Juhamran Department of Surgery, Faculty of Medicine, Muslim University of Indonesia

Keywords:

NLRP3 inflammasome, wound healing

Abstract

Wound healing is a complex biological process involving hemostasis, inflammation, proliferation, and remodeling. One of the key regulators of the inflammatory phase is the NLRP3 inflammasome, a multiprotein complex that plays a role in the activation of caspase-1 and the release of the proinflammatory cytokine interleukin-1.β(IL-1β) and interleukin-18 (IL-18), as well as the induction of pyroptosis. Physiological activation of NLRP3 is required to initiate an immune response, but excessive activation can prolong inflammation and inhibit the wound healing process. Therefore, studying the effect of the NLRP3 inflammasome on wound healing is important as a basis for developing inflammation-modulating therapies. This study used a literature review method by examining 25 scientific articles published in 2022–2026. The literature search was conducted through the PubMed, Google Scholar, ScienceDirect, SpringerLink, Frontiers, Nature Publishing Group, and MDPI databases using keywords related to NLRP3 inflammasome, wound healing, pyroptosis, diabetic wound, and inflammation. Data were analyzed descriptively narratively to identify the mechanism of NLRP3 activation, its role in wound healing, and potential therapies targeting this pathway. The results of the synthesis indicate that the NLRP3 inflammasome plays a crucial role in regulating the inflammatory response during wound healing. Inflammasome activation is required in the early phase for pathogen elimination and clearance of damaged tissue, but excessive activation increases IL-1 production.β, IL-18, and pyroptosis, thereby inhibiting angiogenesis, fibroblast proliferation, collagen deposition, and re-epithelialization. Various studies have shown that modulating NLRP3 using probiotics, natural compounds, hydrogels, stem cell-derived extracellular vesicles, and exosomes can suppress inflammation, enhance tissue regeneration, and accelerate wound healing, especially in diabetic wounds, burns, and radiation injuries. The NLRP3 inflammasome has a dual role in wound healing: it acts as a key regulator of the inflammatory response and as a factor that can inhibit tissue regeneration if overactivated. Modulating NLRP3 activity is a promising therapeutic strategy to accelerate wound healing by controlling inflammation and enhancing tissue regeneration.

References

Chen Y, Ye X, Escames G, Lei W, Zhang X, Li M, et al. The NLRP3 inflammasome: contributions to inflammation-related diseases. Cell Mol Biol Lett. 2023;28:51. doi:10.1186/s11658-023-00475-4.

Fu J, Wu H. Structural mechanisms of NLRP3 inflammasome assembly and activation. Annu Rev Immunol.2024;42:133–160. doi:10.1146/annurev-immunol-081022-021207.

Wang X, Li X, Liu J, Tao Y, Wang T, Li L. Lactobacillus plantarum promotes wound healing by inhibiting the NLRP3 inflammasome and pyroptosis activation in diabetic foot wounds. J Inflamm Res. 2024;17:1835–1851. doi:10.2147/JIR.S449565.

Zhu D, Li J, Yu B, Liu N, Guo X, Su Y, et al. Spatiotemporal regulation of acute wound healing by the NLRP3 inflammasome: dual roles in macrophage-fibroblast chemotaxis and phenotype during wound repair. Burns Trauma. 2025;13:tkag002. doi:10.1093/burnst/tkag002.

Zhao J, Zhang S, Gong Z, Mao W, Bao W, Li Q, et al. NLRP3: a key regulator of skin wound healing and macrophage-fibroblast interactions in mice. J Transl Med. 2025;23:150. doi:10.1186/s12964-025-02063-9.

Al Mamun A, Shao C, Geng P, Wang S, Xiao J. The mechanism of pyroptosis and its application prospect in diabetic wound healing. J Inflamm Res. 2024;17:1607–1625. doi:10.2147/JIR.S448693.

Mu X, Wu X, He W, Liu Y, Wu F, Nie X. Pyroptosis and inflammasomes in diabetic wound healing. Front Endocrinol (Lausanne). 2022;13:950798. doi:10.3389/fendo.2022.950798.

Cheng H, Chen L, Huang M, Hou J, Chen Z, Yang X. Hunting down NLRP3 inflammasome: an executioner of radiation-induced injury. Front Immunol. 2022;13:967989. doi:10.3389/fimmu.2022.967989.

Li X, Luo S, Chen X, Li S, Hao L, Yang D. Adipose-derived stem cells attenuate acne-related inflammation via suppression of NLRP3 inflammasome. Stem Cell Res Ther. 2024;15:198.

Di Filippo M, Karakaya T, Slaufova M, Cheng PF, Hennig P, Boukamp P, et al. NLRP1 inflammasome activation in skin equivalents reveals mechanistic insights into the roles of keratinocytes in psoriasis. Cell Death Dis. 2026;17. doi:10.1038/s41419-026-08908-6.

Honda TSB, Ku J, Anders HJ. Cell type-specific roles of NLRP3, inflammasome-dependent and -independent, in host defense, sterile necroinflammation, tissue repair, and fibrosis. Front Immunol. 2023;14:1214289. doi:10.3389/fimmu.2023.1214289.

Liu Y, Shi L, Qiu W, Shi Y. Ferulic acid exhibits anti-inflammatory effects by inducing autophagy and blocking NLRP3 inflammasome activation. Inflammopharmacology. 2022;30:311–323. doi:10.1007/s13273-021-00219-5.

Xue JC, Yuan S, Hou XT, Meng H, Liu BH, Cheng WW, et al. Natural products modulate NLRP3 in ulcerative colitis. Phytomedicine Plus. 2025;5:100748.

Huang C, Huangfu C, Bai Z, Zhu L, Shen P, Wang N, et al. Multifunctional carbomer based ferulic acid hydrogel promotes wound healing in radiation-induced skin injury by inactivating NLRP3 inflammasome. J Nanobiotechnology. 2024;22:604. doi:10.1186/s12951-024-02789-7.

Li J, Lin X, Wang J, Li X, Zhang Z, Ji L, et al. Dendritic cell repression by TNF-α-primed exosomes accelerate T2DM wound healing through miR-146a-5p/TXNIP/NLRP3 axis. Int J Nanomedicine. 2025;20:3247–3266. doi:10.2147/IJN.S522994.

Feng S, Xie X, Li J, Xu X, Chen C, Zou G, et al. Bile acids induce liver fibrosis through the NLRP3 inflammasome pathway and the mechanism of FXR inhibition of NLRP3 activation. Hepatol Int. 2023;17:1319–1335. doi:10.1007/s12072-023-10610-0.

Li H, Zhao J, Cao L, Luo Q, Zhang C, Zhang L. The NLRP3 inflammasome in burns: a novel potential therapeutic target. Burns Trauma. 2024;12:tkae020. doi:10.1093/burnst/tkae020.

Andriani D, Roestamadji RI, Rahayu RP. Astaxanthin is a promising therapy for wound healing in diabetic conditions: a review. J Int Dent Med Res. 2024;17:1525–1532.

Li Z, Yang Z, Zhu Y, Fu C, Li N, Peng F. Sorcin regulate pyroptosis by interacting with NLRP3 inflammasomes to facilitate the progression of hepatocellular carcinoma. Cell Death Dis. 2023;14:494. doi:10.1038/s41419-023-06096-1.

Zheng Y, Wang S, Zhong Y, Huang C, Wu X. A20 affects macrophage polarization through the NLRP3 inflammasome signaling pathway and promotes breast cancer progression. Exp Ther Med. 2023;25:221. doi:10.3892/etm.2023.11846.

Wang Y, Liu F, Chen L, Fang C, Lin S, Yun S, et al. Neutrophil extracellular traps (NETs) promote non-small cell lung cancer metastasis by suppressing lncRNA MIR503HG to activate the NF-κB/NLRP3 inflammasome pathway. Front Immunol. 2022;13:867516. doi:10.3389/fimmu.2022.867516.

Wang Y, Jing L, Lei X, Mai Z, Li B, Shi Y, et al. Umbilical cord mesenchymal stem cell-derived apoptotic extracellular vesicles ameliorate cutaneous wound healing in type 2 diabetic mice via macrophage pyroptosis inhibition. Stem Cell Res Ther. 2023;14:364. doi:10.1186/s13287-023-03490-6.

Mu X, Wu X, He W, Liu Y, Wu F, Nie X. Pyroptosis and inflammasomes in diabetic wound healing. Front Endocrinol (Lausanne). 2022;13:950798. doi:10.3389/fendo.2022.950798.

Thomas CP, Tyrrell VJ, Burston JJ, Johnson SRC, Aldrovandi M, Alvarez-Jarreta J, et al. 12/15-lipoxygenase orchestrates murine wound healing via PPARγ-activating oxylipins acting holistically to dampen inflammation. Proc Natl Acad Sci U S A. 2025;122:e2502640122. doi:10.1073/pnas.2502640122.

Zhang L, Wang Y, Liu X, Zhang Y. NLRP3 inflammasome activation in MΦs-CRC crosstalk promotes colorectal cancer metastasis. Ann Clin Lab Sci. 2024;54(4):563–572.

Downloads

Published

2026-08-04

How to Cite

Nur Aliviya Ananda, & Reeny Purnamasari Juhamran. (2026). The Effect of NLRP3 Inflammasome on Wound Healing. Jurnal Kesehatan, Rekam Medis Dan Farmasi (JUK-Medifa), 4(02), 124–137. Retrieved from https://jurnal.seaninstitute.or.id/index.php/health/article/view/1112