Skip to main content

Advertisement

SpringerLink
Log in

Focus on the role of NLRP3 inflammasome in the pathology of endometriosis: a review on molecular mechanisms and possible medical applications

  • Review
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

Endometriosis (EMS) is a gynecological disease that leads to pathological conditions, which are connected to the initiation of pro-inflammatory cytokine production. Inflammation plays a vital role in the pathogenesis of EMS. The activation and formation of cytoplasmic inflammasome complexes is considered an important step of inflammation and a key regulator of pyroptosis, a form of cell death. NLR family pyrin domain containing 3 (NLRP3) inflammasome complex modulates innate immune activity and inflammation. The NLRP3 inflammasome activates cysteine protease caspase-1, which produces active pro-inflammatory interleukins (ILs), including IL-1β and IL-18. The aim of this review article was to discuss the involvement of NLRP3 inflammasome assembly and its activation in the pathophysiology of EMS and target related pathways in designing appropriate therapeutic approaches. Dysregulation of sex hormone signaling pathways was associated with over-activation of the NLPR3 inflammasome. In this study, we demonstrated the involvement of NLRP3 inflammasome signaling pathways in the pathophysiology of EMS. The manuscript also discusses the beneficial effects of targeted therapy through synthetic inhibitors of NLRP3 signaling pathways to control EMS lesions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

No datasets were generated or analyzed during the current study.

References

  • Agarwal N, Subramanian A (2010) Endometriosis - morphology, clinical presentations and molecular pathology. J Lab Physicians 2(1):1–9

    Article  PubMed  PubMed Central  Google Scholar 

  • Ahn SH, Khalaj K, Young SL, Lessey BA, Koti M, Tayade C. (2016) Immune-inflammation gene signatures in endometriosis patients. Fertility and sterility 106(6):1420–31. e7

  • Akther M, Haque ME, Park J, Kang T-B, Lee K-H (2021) NLRP3 Ubiquitination-a new approach to target NLRP3 inflammasome activation. Int J Mol Sci 22(16):8780

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Al-Sabbagh M, Lam EW, Brosens JJ (2012) Mechanisms of endometrial progesterone resistance. Mol Cell Endocrinol 358(2):208–215

    Article  CAS  PubMed  Google Scholar 

  • Asghari S, Valizadeh A, Aghebati-Maleki L, Nouri M, Yousefi M (2018) Endometriosis: perspective, lights, and shadows of etiology. Biomed Pharmacother 106:163–174

    Article  PubMed  Google Scholar 

  • Battineni G, Sagaro GG, Chintalapudi N, Amenta F, Tomassoni D (2021) Tayebati SKJIJoMS. Impact of Obesity-Induced Inflammation on Cardiovascular Diseases (CVD) 22(9):4798

    CAS  Google Scholar 

  • Biasizzo M, Kopitar-Jerala N (2020) Interplay between NLRP3 inflammasome and autophagy. Front Immunol 11:2470

    Article  Google Scholar 

  • Bulletti C, Coccia ME, Battistoni S, Borini A (2010) Endometriosis and infertility. J Assist Reprod Genet 27(8):441–447

    Article  PubMed  PubMed Central  Google Scholar 

  • Bullon P, Manuel NJ (2017) Inflammasome as a key pathogenic mechanism in endometriosis. Curr Drug Targets 18(9):997–1002

    Article  CAS  PubMed  Google Scholar 

  • Bulun SE, Monsavais D, Pavone ME, Dyson M, Xue Q, Attar E, et al. editors. (2012) Role of estrogen receptor-β in endometriosis. Seminars in reproductive medicine; 2012: Thieme Medical Publishers

  • Chan AH, Schroder K (2020) Inflammasome signaling and regulation of interleukin-1 family cytokines. J Exp Med 217(1):e20190314

    Article  PubMed  Google Scholar 

  • Choi J, Jo M, Lee E, Kim SE, Lee D-Y, Choi D. (2022) Inhibition of the NLRP3 inflammasome by progesterone is attenuated by abnormal autophagy induction in endometriotic cyst stromal cells: implications for endometriosis. Molecular human reproduction 28(4):gaac007

  • Cordone V, Ferrara F, Pecorelli A, Guiotto A, Vitale A, Amicarelli F et al (2022) The constitutive activation of TLR4-IRAK1- NFκB axis is involved in the early NLRP3 inflammasome response in peripheral blood mononuclear cells of Rett syndrome patients. Free Radical Biol Med 181:1–13

    Article  CAS  Google Scholar 

  • Cosin-Roger J, Simmen S, Melhem H, Atrott K, Frey-Wagner I, Hausmann M et al (2017) Hypoxia ameliorates intestinal inflammation through NLRP3/mTOR downregulation and autophagy activation. Nat Commun 8(1):1–13

    Article  CAS  Google Scholar 

  • Dai S, Zhu M, Wu R, Lin D, Huang Z, Ren L et al (2019) Lipoxin A4 suppresses IL-1β-Induced Cyclooxygenase-2 expression through inhibition of p38 MAPK activation in endometriosis. Reprod Sci 26(12):1640–1649

    Article  CAS  PubMed  Google Scholar 

  • D'Amico R, Fusco R, Cordaro M, Siracusa R, Peritore AF, Gugliandolo E, et al. Modulation of NLRP3 inflammasome through formyl peptide receptor 1 (Fpr-1) pathway as a new therapeutic target in bronchiolitis obliterans syndrome. Int J Mol Sci 21(6)

  • Dehoux J-P, Defrère S, Squifflet J, Donnez O, Polet R, Mestdagt M, et al. (2011) Is the baboon model appropriate for endometriosis studies? Fertility and sterility 96(3):728–33. e3

  • Dominic A, Le N-T, Takahashi M (2022) Loop between NLRP3 inflammasome and reactive oxygen species. Antioxid Redox Signal 36(10):784–796

    Article  CAS  PubMed  Google Scholar 

  • Dyson MT, Bulun SE (2012) Cutting SRC-1 down to size in endometriosis. Nat Med 18(7):1016–1018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Eisenberg VH, Zolti M, Soriano D (2012) Is there an association between autoimmunity and endometriosis? Autoimmun Rev 11(11):806–814

    Article  CAS  PubMed  Google Scholar 

  • Elieh Ali Komi D, Wöhrl S, Bielory L (2020) Mast cell biology at molecular level: a comprehensive review. Clinical reviews in allergy & immunology 58(3):342–65

  • Ellis K, Munro D, Clarke J (2022) Endometriosis is undervalued: a call to action. frontiers in global women's health 3

  • Fainaru O, Adini A, Benny O, Adini I, Short S, Bazinet L et al (2008) Dendritic cells support angiogenesis and promote lesion growth in a murine model of endometriosis. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology 22(2):522–529

    Article  CAS  PubMed  Google Scholar 

  • Fang X, Wang Y, Zhang Y, Li Y, Kwak-Kim J, Wu L (2021) NLRP3 inflammasome and its critical role in gynecological disorders and obstetrical complications. Frontiers in Immunology :3599

  • Foti PV, Farina R, Palmucci S, Vizzini IAA, Libertini N, Coronella M et al (2018) Endometriosis: clinical features, MR imaging findings and pathologic correlation. Insights Imaging 9(2):149–172

    Article  PubMed  PubMed Central  Google Scholar 

  • Franchi L, Eigenbrod T, Muñoz-Planillo R, Nuñez G (2009) The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol 10(3):241–247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fukui A, Mai C, Saeki S, Yamamoto M, Takeyama R, Kato T, et al. (2021) Pelvic endometriosis and natural killer cell immunity. American journal of reproductive immunology (New York, NY : 1989) 85(4):e13342

  • Fuldeore MJ, Soliman AM (2017) Prevalence and symptomatic burden of diagnosed endometriosis in the United States: national estimates from a cross-sectional survey of 59,411 Women. Gynecol Obstet Invest 82(5):453–461

    Article  PubMed  Google Scholar 

  • Fusco R, D’Amico R, Cordaro M, Gugliandolo E, Siracusa R, Peritore AF et al (2018) Absence of formyl peptide receptor 1 causes endometriotic lesion regression in a mouse model of surgically-induced endometriosis. Oncotarget 9(59):31355–31366

    Article  PubMed  PubMed Central  Google Scholar 

  • Fusco R, Siracusa R, Genovese T, Cuzzocrea S, Di Paola R (2020) Focus on the role of NLRP3 inflammasome in diseases. Int J Mol Sci 21(12):4223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • García-Gómez E, Vázquez-Martínez ER, Reyes-Mayoral C, Cruz-Orozco OP, Camacho-Arroyo I, Cerbón M (2020) Regulation of inflammation pathways and inflammasome by sex steroid hormones in endometriosis. Front Endocrinol (Lausanne). 10:935

  • Guo S-W (2020) Cancer-associated mutations in endometriosis: shedding light on the pathogenesis and pathophysiology. Hum Reprod Update 26(3):423–449

    Article  PubMed  Google Scholar 

  • Guo S-W, Du Y, Liu X (2016) Platelet-derived TGF-β1 mediates the down-modulation of NKG2D expression and may be responsible for impaired natural killer (NK) cytotoxicity in women with endometriosis. Hum Reprod 31(7):1462–1474

    Article  CAS  PubMed  Google Scholar 

  • Guo M, Bafligil C, Tapmeier T, Hubbard C, Manek S, Shang C et al (2020) Mass cytometry analysis reveals a distinct immune environment in peritoneal fluid in endometriosis: a characterisation study. BMC Med 18(1):3

    Article  PubMed  PubMed Central  Google Scholar 

  • Guo X, Xu X, Li T, Yu Q, Wang J, Chen Y, et al. (2021) NLRP3 inflammasome activation of mast cells by estrogen via the nuclear-initiated signaling pathway contributes to the development of endometriosis. Frontiers in immunology. 2021;12:749979

  • Hafner-Bratkovič I, Pelegrín P (2018) Ion homeostasis and ion channels in NLRP3 inflammasome activation and regulation. Curr Opin Immunol 52:8–17

    Article  PubMed  Google Scholar 

  • Han SJ, Jung SY, Wu S-P, Hawkins SM, Park MJ, Kyo S et al (2015) Estrogen receptor β modulates apoptosis complexes and the inflammasome to drive the pathogenesis of endometriosis. Cell 163(4):960–974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hang Y, Tan L, Chen Q, Liu Q, Jin Y (2021) E3 ubiquitin ligase TRIM24 deficiency promotes NLRP3/caspase-1/IL-1β-mediated pyroptosis in endometriosis. Cell Biol Int 45(7):1561–1570

    Article  CAS  PubMed  Google Scholar 

  • Heard ME, Melnyk SB, Simmen FA, Yang Y, Pabona JMP, Simmen RCJE (2016) High-fat diet promotion of endometriosis in an immunocompetent mouse model is associated with altered peripheral and ectopic lesion redox and inflammatory status 157(7):2870-82

  • Herath S, Fischer DP, Werling D, Williams EJ, Lilly ST, Dobson H, et al. (2006) Expression and function of Toll-like receptor 4 in the endometrial cells of the uterus 147(1):562–70

  • Ho HN, Wu MY, Yang YS (1997) Peritoneal cellular immunity and endometriosis. American journal of reproductive immunology (New York, NY : 1989). 38(6):400–12

  • Hogg C, Horne AW, Greaves E (2020) Endometriosis-associated macrophages: origin, phenotype, and function. Front Endocrinol (lausanne) 11:7

    Article  PubMed  Google Scholar 

  • Huang F, Cao J, Liu Q, Zou Y, Li H, Yin T (2013) MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1β induced in human endometriosis stromal cells in vitro. Int J Clin Exp Pathol 6(10):2129

    PubMed  PubMed Central  Google Scholar 

  • Hussein M, Chai DC, Kyama CM, Mwenda JM, Palmer SS, Gotteland J-P, et al. (2016) c-Jun NH2-terminal kinase inhibitor bentamapimod reduces induced endometriosis in baboons: an assessor-blind placebo-controlled randomized study 105(3):815–24. e5

  • Ito F, Yamada Y, Shigemitsu A, Akinishi M, Kaniwa H, Miyake R, et al. (2017) Role of oxidative stress in epigenetic modification in endometriosis 24(11):1493-502

  • Izumi G, Koga K, Takamura M, Makabe T, Satake E, Takeuchi A et al (2018) Involvement of immune cells in the pathogenesis of endometriosis. J Obstet Gynaecol Res 44(2):191–198

    Article  PubMed  Google Scholar 

  • Johnson NP, Hummelshoj L, Consortium WESM, Abrao M, Adamson G, Allaire C, et al. (2013) Consensus on current management of endometriosis. Human reproduction 28(6):1552–68

  • Jorquera G, Russell J, Monsalves-Álvarez M, Cruz G, Valladares-Ide D, Basualto-Alarcón C, et al. (2021) NLRP3 inflammasome: potential role in obesity related low-grade inflammation and insulin resistance in skeletal muscle 22(6):3254

  • Juliana C, Fernandes-Alnemri T, Wu J, Datta P, Solorzano L, Yu J-W et al (2010) Anti-inflammatory compounds parthenolide and Bay 11–7082 are direct inhibitors of the inflammasome. J Biol Chem 285(13):9792–9802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kajihara H, Yamada Y, Kanayama S, Furukawa N, Noguchi T, Haruta S, et al. (2011) New insights into the pathophysiology of endometriosis: from chronic inflammation to danger signal. 27(2):73-9

  • Kapoor R, Stratopoulou CA, Dolmans M-M (2021) Pathogenesis of endometriosis: new insights into prospective therapies. Int J Mol Sci 22(21):11700

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kawai T, Akira S (2007) Signaling to NF-kappaB by Toll-like receptors. Trends Mol Med 13(11):460–469

    Article  CAS  PubMed  Google Scholar 

  • Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Frontiers in immunology. 2014:461.

  • Kelley N, Jeltema D, Duan Y, He Y (2019) The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int J Mol Sci 20(13):3328

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khan KN, Yamamoto K, Fujishita A, Muto H, Koshiba A, Kuroboshi H et al (2019) Differential levels of regulatory T cells and T-helper-17 cells in women with early and advanced endometriosis. J Clin Endocrinol Metab 104(10):4715–4729

    Article  PubMed  Google Scholar 

  • Khan KN, Kitajima M, Hiraki K, Yamaguchi N, Katamine S, Matsuyama T, et al. (2010) Escherichia coli contamination of menstrual blood and effect of bacterial endotoxin on endometriosis. 94(7):2860–3. e3

  • Kim EH, Park MJ, Park S, Lee ES (2015) Increased expression of the NLRP3 inflammasome components in patients with Behçet’s disease. Journal of Inflammation (london, England) 12:41

    Article  PubMed  Google Scholar 

  • Kusama K, Fukushima Y, Yoshida K, Sakakibara H, Tsubata N, Yoshie M, et al. (2021) Endometrial epithelial-mesenchymal transition (EMT) by menstruation-related inflammatory factors during hypoxia. Molecular human reproduction 27(6)

  • Lee C, Do HTT, Her J, Kim Y, Seo D, Rhee I (2019) Inflammasome as a promising therapeutic target for cancer. Life Sci 231:116593

    Article  CAS  PubMed  Google Scholar 

  • Li T, Wang J, Guo X, Yu Q, Ding S, Xu X, et al. (2020) Possible involvement of crosstalk between endometrial cells and mast cells in the development of endometriosis via CCL8/CCR1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 129:110476

  • Li D, Wu M (2021) Pattern recognition receptors in health and diseases. Signal Transduct Target Ther 6(1):291

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin Y-H, Chen Y-H, Chang H-Y, Au H-K, Tzeng C-R, Huang Y-H (2018) Chronic niche inflammation in endometriosis-associated infertility: current understanding and future therapeutic strategies. Int J Mol Sci 19(8):2385

    Article  PubMed  PubMed Central  Google Scholar 

  • Liu Y, Liang S, Yang F, Sun Y, Niu L, Ren Y et al (2020) Biological characteristics of endometriotic mesenchymal stem cells isolated from ectopic lesions of patients with endometriosis. Stem Cell Res Ther 11(1):346

    Article  PubMed  PubMed Central  Google Scholar 

  • Lyons DO, Pullen NA (2020) Beyond IgE: alternative mast cell activation across different disease states. Int J Mol Sci. 2020;21(4)

  • Macer ML, Taylor HS (2012) Endometriosis and infertility: a review of the pathogenesis and treatment of endometriosis-associated infertility. Obstetrics and Gynecology Clinics 39(4):535–549

    PubMed  Google Scholar 

  • Machairiotis N, Vasilakaki S, Thomakos N (2021) Inflammatory mediators and pain in endometriosis: a systematic review. Biomedicines 9(1):54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malutan AM, Drugan T, Costin N, Ciortea R, Bucuri C, Rada MP et al (2015) Pro-inflammatory cytokines for evaluation of inflammatory status in endometriosis. Cent Eur J Immunol 40(1):96–102

    Article  PubMed  PubMed Central  Google Scholar 

  • Mathiak G, Grass G, Herzmann T, Luebke T, Zetina CC, Boehm SA et al (2000) Caspase-1-inhibitor ac-YVAD-cmk reduces LPS-lethality in rats without affecting haematology or cytokine responses. Br J Pharmacol 131(3):383–386

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mehrannia K, Mokhtari T, Mogehi SMHN, Akbari M, Bazzaz JT, Mahakizeh S, et al. (2018) Intracerebroventricular injection of Wharton’s jelly mesenchymal stem cells attenuates brain damage in rat model of hypoxia: optimization of vascular endothelial growth factor and downregulation of inflammatory factors. J Contemp Med Sci| 4(3):134–9

  • Mishra AR, Zheng J, Tang X, Goering PL (2016) Silver nanoparticle-induced autophagic-lysosomal disruption and NLRP3-inflammasome activation in HepG2 cells is size-dependent. Toxicol Sci 150(2):473–487

    Article  CAS  PubMed  Google Scholar 

  • Mishra SR, Mahapatra KK, Behera BP, Patra S, Bhol CS, Panigrahi DP et al (2021) Mitochondrial dysfunction as a driver of NLRP3 inflammasome activation and its modulation through mitophagy for potential therapeutics. Int J Biochem Cell Biol 136:106013

    Article  CAS  PubMed  Google Scholar 

  • Missmer SA, Chavarro JE, Malspeis S, Bertone-Johnson ER, Hornstein MD, Spiegelman D et al (2010) A Prospective Study of Dietary Fat Consumption and Endometriosis Risk 25(6):1528–1535

    CAS  Google Scholar 

  • Mohammed I, Ijaz S, Mokhtari T, Gholaminejhad M, Mahdavipour M, Jameie B et al (2020) Subventricular zone-derived extracellular vesicles promote functional recovery in rat model of spinal cord injury by inhibition of NLRP3 inflammasome complex formation. Metab Brain Dis 35(5):809–818

    Article  CAS  PubMed  Google Scholar 

  • Murakami M, Osuka S, Muraoka A, Hayashi S, Bayasula, Kasahara Y, et al. (2022) Effectiveness of NLRP3 inhibitor as a non-hormonal treatment for ovarian endometriosis. Reproductive Biology and Endocrinology 20(1):58

  • Nagai T, Ishida C, Nakamura T, Iwase A, Mori M, Murase T et al (2020) Focal adhesion kinase-mediated sequences, including cell adhesion, inflammatory response, and fibrosis, as a therapeutic target in endometriosis. Reprod Sci 27(7):1400–1410

    Article  CAS  PubMed  Google Scholar 

  • Nava-González EJ, de la Garza-Casas YE, Salazar-Montalvo RG, Gallegos-Cabriales EC (2013) Relationship among anthropometric and gluco-metabolic parameters, bone mineral density and endometriosis. Revista Medica Del Instituto Mexicano Del Seguro Social 51(5):522–531

    PubMed  Google Scholar 

  • Ness RB, Soper DE, Holley RL, Peipert J, Randall H, Sweet RL et al (2002) Effectiveness of inpatient and outpatient treatment strategies for women with pelvic inflammatory disease: results from the Pelvic Inflammatory Disease Evaluation and Clinical Health (PEACH) randomized trial. Am J Obstet Gynecol 186(5):929–937

    Article  PubMed  Google Scholar 

  • Olkowska-Truchanowicz J, Bocian K, Maksym RB, Białoszewska A, Włodarczyk D, Baranowski W et al (2013) CD4+ CD25+ FOXP3+ regulatory T cells in peripheral blood and peritoneal fluid of patients with endometriosis. Human Reproduction (oxford, England) 28(1):119–124

    Article  CAS  PubMed  Google Scholar 

  • Palmer SS, Altan M, Denis D, Tos EG, Gotteland JP, Osteen KG et al (2016) Bentamapimod (JNK inhibitor AS602801) induces regression of endometriotic lesions in animal models. Reproductive Sciences (thousand Oaks, Calif) 23(1):11–23

    Article  CAS  PubMed  Google Scholar 

  • Parasar P, Ozcan P, Terry KL (2017) Endometriosis: epidemiology, diagnosis and clinical management. Curr Obstet Gynecol Rep 6(1):34–41

    Article  PubMed  PubMed Central  Google Scholar 

  • Parkin KL, Fazleabas AT (2016) Uterine leukocyte function and dysfunction: a hypothesis on the impact of endometriosis. Am J Reprod Immunol 75(3):411–417

    Article  PubMed  PubMed Central  Google Scholar 

  • Patel BG, Lenk EE, Lebovic DI, Shu Y, Yu J, Taylor RN (2018) Pathogenesis of endometriosis: Interaction between endocrine and inflammatory pathways. Best Pract Res Clin Obstet Gynaecol 50:50–60

    Article  PubMed  Google Scholar 

  • Piccinini AM, Midwood KS (2010) DAMPening inflammation by modulating TLR signalling. Mediators of inflammation 2010

  • Prescott J, Farland L, Tobias D, Gaskins A, Spiegelman D, Chavarro J et al (2016) A prospective cohort study of endometriosis and subsequent risk of infertility. Hum Reprod 31(7):1475–1482

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rafique S, Decherney AH (2017) Medical management of endometriosis. Clin Obstet Gynecol 60(3):485–496

    Article  PubMed  PubMed Central  Google Scholar 

  • de Rivero Vaccari JP. The inflammasome in reproductive biology: a promising target for novel therapies. Front Endocrinol (Lausanne). 2020:8.

  • Rocha ALL, Reis FM, Taylor RN (2013) Angiogenesis and endometriosis. Obstetrics and gynecology international 2013

  • Sagulenko V, Thygesen SJ, Sester DP, Idris A, Cridland JA, Vajjhala PR et al (2013) AIM2 and NLRP3 inflammasomes activate both apoptotic and pyroptotic death pathways via ASC. Cell Death Differ 20(9):1149–1160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salliss ME, Farland LV, Mahnert ND, Herbst-Kralovetz MM (2022) The role of gut and genital microbiota and the estrobolome in endometriosis, infertility and chronic pelvic pain. Hum Reprod Update 28(1):92–131

    Article  CAS  Google Scholar 

  • Santoni G, Cardinali C, Morelli MB, Santoni M, Nabissi M, Amantini C (2015) Danger- and pathogen-associated molecular patterns recognition by pattern-recognition receptors and ion channels of the transient receptor potential family triggers the inflammasome activation in immune cells and sensory neurons. J Neuroinflammation 12(1):21

    Article  PubMed  PubMed Central  Google Scholar 

  • Schmidt RL, Lenz LL. (2012) Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activation

  • Schuh E, Groß CJ, Wagner D, Schlüter M, Groß O, Kümpfel T (2019) MCC950 blocks enhanced interleukin-1β production in patients with NLRP3 low penetrance variants. Clinical Immunology (orlando, Fla) 203:45–52

    Article  CAS  PubMed  Google Scholar 

  • Seok JK, Kang HC, Cho Y-Y, Lee HS, Lee JY (2021) Regulation of the NLRP3 inflammasome by post-translational modifications and small molecules. Front Immunol 11:3877

    Article  Google Scholar 

  • Shah DK, Correia KF, Vitonis AF, Missmer SAJHR (2013) Body size and endometriosis: results from 20 years of follow-up within the Nurses' Health Study II prospective cohort 28(7):1783–92

  • Shao B-Z, Xu Z-Q, Han B-Z, Su D-F, Liu C (2015) NLRP3 inflammasome and its inhibitors: a review. Front Pharmacol. 6:262

  • Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z (2011) Role of natural killer cell activity in the pathogenesis of endometriosis. Curr Med Chem 18(2):200–208

    Article  CAS  PubMed  Google Scholar 

  • Sikora J, Mielczarek-Palacz A, Kondera-Anasz Z (2012) Imbalance in cytokines from interleukin-1 family–role in pathogenesis of endometriosis. Am J Reprod Immunol 68(2):138–145

    Article  CAS  PubMed  Google Scholar 

  • Sikora J, Smycz-Kubańska M, Mielczarek-Palacz A, Bednarek I, Kondera-Anasz Z (2018) The involvement of multifunctional TGF-β and related cytokines in pathogenesis of endometriosis. Immunol Lett 201:31–37

    Article  CAS  PubMed  Google Scholar 

  • Song N, Li T. Regulation of NLRP3 inflammasome by phosphorylation. Frontiers in immunology. 2018a:2305.

  • Song N, Li T (2018b) Regulation of NLRP3 inflammasome by phosphorylation. Front Immunol 9:2305

    Article  PubMed  PubMed Central  Google Scholar 

  • Symons LK, Miller JE, Kay VR, Marks RM, Liblik K, Koti M et al (2018) The immunopathophysiology of endometriosis. Trends Mol Med 24(9):748–762

    Article  CAS  PubMed  Google Scholar 

  • Vallée A, Lecarpentier Y (2020) Curcumin and endometriosis. Int J Mol Sci 21(7):2440

    Article  PubMed  PubMed Central  Google Scholar 

  • Vallvé-Juanico J, Houshdaran S, Giudice LC (2019) The endometrial immune environment of women with endometriosis. Hum Reprod Update 25(5):564–591

    Article  PubMed  Google Scholar 

  • Walenta L, Schmid N, Schwarzer JU, Köhn F-M, Urbanski HF, Behr R et al (2018) NLRP3 in somatic non-immune cells of rodent and primate testes. Reproduction 156(3):231–238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Z, Zhang S, Xiao Y, Zhang W, Wu S, Qin T, et al. (2020) NLRP3 inflammasome and inflammatory diseases. Oxidative medicine and cellular longevity 2020

  • Williams A, Flavell RA, Eisenbarth SC (2010) The role of NOD-like receptors in shaping adaptive immunity. Curr Opin Immunol 22(1):34–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Wang H, Kouadir M, Song H, Shi F (2019) Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors. Cell Death Dis 10(2):128

    Article  PubMed  PubMed Central  Google Scholar 

  • Yen H, Karino M, Tobe TJFiC (2016) Microbiology I. Modulation of the inflammasome signaling pathway by enteropathogenic and enterohemorrhagic Escherichia coli 6:89

  • Yilmaz BD, Bulun SE (2019) Endometriosis and nuclear receptors. Hum Reprod Update 25(4):473–485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao J, Ma W, Chen W, Gao J, Li C, Tong Y et al (2019) AEG-1 aggravates inflammation via promoting NALP3 inflammasome formation in murine endometriosis lesions. Animal Cells and Systems 23(6):407–413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou F, Li C, Zhang S-Y (2021) NLRP3 inflammasome: a new therapeutic target for high-risk reproductive disorders? Chin Med J 134(01):20–27

    Article  CAS  Google Scholar 

  • Zhou F, Zhao F, Huang Q, Lin X, Zhang S, Dai Y (2022) NLRP3 activated macrophages promote endometrial stromal cells migration in endometriosis. J Reproduct Immunol. 103649

  • Zhu TH, Zou G, Ding SJ, Li TT, Zhu LB, Wang JZ et al (2019) Mast cell stabilizer ketotifen reduces hyperalgesia in a rodent model of surgically induced endometriosis. J Pain Res 12:1359–1369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zou G, Wang J, Xu X, Xu P, Zhu L, Yu Q, et al. (2021) Cell subtypes and immune dysfunction in peritoneal fluid of endometriosis revealed by single-cell RNA-sequencing. Cell Biosci. 11(1):98

Download references

Author information

Authors and Affiliations

  1. Department of Gynecology and Obstetrics, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Elnaz Irandoost, Shaparak Najibi, Saba Talebbeigi & Saina Nassiri

Authors
  1. Elnaz Irandoost
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shaparak Najibi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Saba Talebbeigi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Saina Nassiri
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EI and SN conceived the presented idea. All the authors equally participated in drafting the article. EI and SN participated in revising it critically for important intellectual content. All the authors gave final approval of the version to be submitted and any revised version.

Corresponding author

Correspondence to Saina Nassiri.

Ethics declarations

Ethical approval

N/A.

Consent to participate

N/A.

Consent for publication

N/A.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Irandoost, E., Najibi, S., Talebbeigi, S. et al. Focus on the role of NLRP3 inflammasome in the pathology of endometriosis: a review on molecular mechanisms and possible medical applications. Naunyn-Schmiedeberg's Arch Pharmacol 396, 621–631 (2023). https://doi.org/10.1007/s00210-022-02365-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00210-022-02365-6

Keywords

Search

Navigation