S100A12蛋白在哮喘中的研究進展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

甘家琦 ,  李超乾

廣西醫科大學第一附屬醫院呼吸內科（廣西南寧 530021）;

Corresponding?author：

李超乾, Email: lichaoqiangood@163.com

Keywords：

DOI：

10.7507/1671-6205.202412039

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Citation： 甘家琦, 李超乾. S100A12蛋白在哮喘中的研究進展. Chinese Journal of Respiratory and Critical Care Medicine, 2025, 24(11): 821-825. doi: 10.7507/1671-6205.202412039 Copy

1.	Sreejit G, Flynn MC, Patil M, et al. S100 family proteins in inflammation and beyond. Adv Clin Chem, 2020, 98: 173-231.
2.	Carvalho A, Lu J, Francis JD, et al. S100A12 in digestive diseases and health: a scoping review. Gastroenterol Res Pract, 2020, 2020: 2868373.
3.	Xia P, Ji X, Yan L, et al. Roles of S100A8, S100A9 and S100A12 in infection, inflammation and immunity. Immunology, 2024, 171(3): 365-376.
4.	Goyette J, Geczy CL. Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids, 2011, 41(4): 821-842.
5.	Foell D, Wittkowski H, Kessel C, et al. Proinflammatory S100A12 can activate human monocytes via Toll-like receptor 4. Am J Respir Crit Care Med, 2013, 187(12): 1324-1334.
6.	Zhang Y, Li Z, Chen C, et al. S100A12 is involved in the pathology of osteoarthritis by promoting M1 macrophage polarization via the NF-κB pathway. Connect Tissue Res, 2024, 65(2): 133-145.
7.	Kim DH, Gu A, Lee JS, et al. Suppressive effects of S100A8 and S100A9 on neutrophil apoptosis by cytokine release of human bronchial epithelial cells in asthma. Int J Med Sci, 2020, 17(4): 498-509.
8.	Curran CS, Bertics PJ. Human eosinophils express RAGE, produce RAGE ligands, exhibit PKC-delta phosphorylation and enhanced viability in response to the RAGE ligand, S100B. Int Immunol, 2011, 23(12): 713-728.
9.	Shen Y, Ye X, Jiang L, et al. Inhibition of S100A12 Attenuates LPS-Induced Endothelial Barrier Dysfunction in HPMECs through the JAK2/STAT3 Signaling Pathway. Curr Mol Med, 2025:.
10.	Wu Y, Zhang W, Gunst SJ. S100A4 is secreted by airway smooth muscle tissues and activates inflammatory signaling pathways via receptors for advanced glycation end products. Am J Physiol Lung Cell Mol Physiol, 2020, 319(1): L185-l195.
11.	Farokhzadian J, Mangolian Shahrbabaki P, Bagheri V. S100A12-CD36 axis: A novel player in the pathogenesis of atherosclerosis? Cytokine, 2019, 122: 154104.
12.	Donato R, Cannon BR, Sorci G, et al. Functions of S100 proteins. Curr Mol Med, 2013, 13(1): 24-57.
13.	Mishra V, Banga J, Silveyra P. Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets. Pharmacol Ther, 2018, 181: 169-182.
14.	Jie Z, Liang Y, Yi P, et al. Retinoic acid regulates immune responses by promoting IL-22 and modulating S100 proteins in viral hepatitis. J Immunol, 2017, 198(9): 3448-3460.
15.	Yang Z, Yan WX, Cai H, et al. S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol, 2007, 119(1): 106-114.
16.	Lin Q, Ni H, Zhong J, et al. Identification of hub genes and potential biomarkers of neutrophilic asthma: evidence from a bioinformatics analysis. J Asthma, 2023, 60(2): 348-359.
17.	Yan Q, Zhang X, Xie Y , et al. Bronchial epithelial transcriptomics and experimental validation reveal asthma severity-related neutrophilc signatures and potential treatments. Commun Biol, 2024, 7(1): 181.
18.	Dong N, Wang Y. MiR-30a Regulates S100A12-induced Retinal Microglial Activation and Inflammation by Targeting NLRP3. Curr Eye Res, 2019, 44(11): 1236-1243.
19.	Lin K, Wang T, Tang Q, et al. IL18R1-related molecules as biomarkers for asthma severity and prognostic markers for idiopathic pulmonary fibrosis. J Proteome Res, 2023, 22(10): 3320-3331.
20.	Gkavogiannakis NA, Tsoporis JN, Drosatos IA, et al. Emergent Inflammatory Markers and Echocardiographic Indices in Patients with Bronchial Asthma. Biomolecules, 2023, 13(6): 955.
21.	Chen M, Ge Y, Lin W, et al. Clinical features and nasal inflammation in asthma and allergic rhinitis. Clin Exp Immunol, 2022, 208(1): 25-32.
22.	Yao L, Zhao H, Tang H, et al. The receptor for advanced glycation end products is required for β-catenin stabilization in a chemical-induced asthma model. Br J Pharmacol, 2016, 173(17): 2600-2613.
23.	Hofmann Bowman MA, Heydemann A, Gawdzik J, et al. Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation. Clin Exp Allergy, 2011, 41(6): 878-889.
24.	Camoretti-Mercado B, Karrar E, Nu?ez L, et al. S100A12 and the airway smooth muscle: beyond inflammation and constriction. J Allergy Ther, 2012, 3(Suppl 1): S1-007.
25.	Zheng J, Dong H, Zhang T, et al. Development and validation of a novel gene signature for predicting the prognosis of idiopathic pulmonary fibrosis based on three epithelial-mesenchymal transition and immune-related genes. Front Genet, 2022, 13: 865052.
26.	Zhang Z, Han N, Shen Y. S100A12 promotes inflammation and cell apoptosis in sepsis-induced ARDS via activation of NLRP3 in?ammasome signaling. Mol Immunol, 2020, 122: 38-48.
27.	Kang JH, Hwang SM, Chung IY. S100A8, S100A9 and S100A12 activate airway epithelial cells to produce MUC5AC via extracellular signal-regulated kinase and nuclear factor-κB pathways. Immunology, 2015, 144(1): 79-90.
28.	Kim K, Kim HJ, Binas B, et al. Inflammatory mediators ATP and S100A12 activate the NLRP3 inflammasome to induce MUC5AC production in airway epithelial cells. Biochem Biophys Res Commun, 2018, 503(2): 657-664.
29.	Jiang W, Wang Z, Hu Z, et al. Blocking the ERK1/2 signal pathway can inhibit S100A12 induced human aortic smooth muscle cells damage. Cell Biol Int, 2017, 41(12): 1307-1315.
30.	Mottais A, Riberi L, Falco A, et al. Epithelial-mesenchymal transition mechanisms in chronic airway diseases: a common process to target? Int J Mol Sci, 2023, 24(15): 12412.
31.	Hofmann Bowman M, Wilk J, Heydemann A, et al. S100A12 mediates aortic wall remodeling and aortic aneurysm. Circ Res, 2010, 106(1): 145-154.
32.	Tondera C, Laube M, Pietzsch J. Insights into binding of S100 proteins to scavenger receptors: class B scavenger receptor CD36 binds S100A12 with high affinity. Amino Acids, 2017, 49(1): 183-191.
33.	Grum-Schwensen B, Klingelh?fer J, Beck M, et al. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance. BMC Cancer, 2015, 15: 44.
34.	Akirav EM, Henegariu O, Preston-Hurlburt P, et al. The receptor for advanced glycation end products (RAGE) affects T cell differentiation in OVA induced asthma. PLoS One, 2014, 9(4): e95678.
35.	Mo S, Yan S, Li J, et al. S100A4 reprofiles lipid metabolism in mast cells via RAGE and PPAR-γ signaling pathway. Int Immunopharmacol, 2024, 128: 111555.
36.	Liu S, Zhang H, Li Y, et al. S100A4 enhances protumor macrophage polarization by control of PPAR-γ-dependent induction of fatty acid oxidation. J Immunother Cancer, 2021, 9(6): e002548.
37.	Son SE, Im DS. Activation of G p rotein-coupled estrogen receptor 1 (GPER) attenuates obesity-induced asthma by switching M1 macrophages to M2 macrophages. Int J Mol Sci, 2024, 25(17): 9532.
38.	Rouleau P, Vandal K, Ryckman C, et al. The calcium-binding protein S100A12 induces neutrophil adhesion, migration, and release from bone marrow in mouse at concentrations similar to those found in human inflammatory arthritis. Clin Immunol, 2003, 107(1): 46-54.
39.	Yang Y, Jiao YY, Zhang Z, et al. Neutrophil extracellular trap is an important connection between hemodialysis and acute myocardial infarction. Ren Fail, 2023, 45(1): 2216307.
40.	Nishida M, Saegusa J, Tanaka S, et al. S100A12 facilitates osteoclast differentiation from human monocytes. PLoS One, 2018, 13(9): e0204140.
41.	Gao J, Liu J, Lu J, et al. SKAP1 expression in cancer cells enhances colon tumor growth and impairs cytotoxic immunity by promoting neutrophil extracellular trap formation via the NFATc1/CXCL8 axis. Adv Sci (Weinh), 2024, 11(41): e2403430.
42.	Quoc QL, Choi Y, Thi Bich TC, et al. S100A9 in adult asthmatic patients: a biomarker for neutrophilic asthma. Exp Mol Med, 2021, 53(7): 1170-1179.

1. Sreejit G, Flynn MC, Patil M, et al. S100 family proteins in inflammation and beyond. Adv Clin Chem, 2020, 98: 173-231.
2. Carvalho A, Lu J, Francis JD, et al. S100A12 in digestive diseases and health: a scoping review. Gastroenterol Res Pract, 2020, 2020: 2868373.
3. Xia P, Ji X, Yan L, et al. Roles of S100A8, S100A9 and S100A12 in infection, inflammation and immunity. Immunology, 2024, 171(3): 365-376.
4. Goyette J, Geczy CL. Inflammation-associated S100 proteins: new mechanisms that regulate function. Amino Acids, 2011, 41(4): 821-842.
5. Foell D, Wittkowski H, Kessel C, et al. Proinflammatory S100A12 can activate human monocytes via Toll-like receptor 4. Am J Respir Crit Care Med, 2013, 187(12): 1324-1334.
6. Zhang Y, Li Z, Chen C, et al. S100A12 is involved in the pathology of osteoarthritis by promoting M1 macrophage polarization via the NF-κB pathway. Connect Tissue Res, 2024, 65(2): 133-145.
7. Kim DH, Gu A, Lee JS, et al. Suppressive effects of S100A8 and S100A9 on neutrophil apoptosis by cytokine release of human bronchial epithelial cells in asthma. Int J Med Sci, 2020, 17(4): 498-509.
8. Curran CS, Bertics PJ. Human eosinophils express RAGE, produce RAGE ligands, exhibit PKC-delta phosphorylation and enhanced viability in response to the RAGE ligand, S100B. Int Immunol, 2011, 23(12): 713-728.
9. Shen Y, Ye X, Jiang L, et al. Inhibition of S100A12 Attenuates LPS-Induced Endothelial Barrier Dysfunction in HPMECs through the JAK2/STAT3 Signaling Pathway. Curr Mol Med, 2025:.
10. Wu Y, Zhang W, Gunst SJ. S100A4 is secreted by airway smooth muscle tissues and activates inflammatory signaling pathways via receptors for advanced glycation end products. Am J Physiol Lung Cell Mol Physiol, 2020, 319(1): L185-l195.
11. Farokhzadian J, Mangolian Shahrbabaki P, Bagheri V. S100A12-CD36 axis: A novel player in the pathogenesis of atherosclerosis? Cytokine, 2019, 122: 154104.
12. Donato R, Cannon BR, Sorci G, et al. Functions of S100 proteins. Curr Mol Med, 2013, 13(1): 24-57.
13. Mishra V, Banga J, Silveyra P. Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets. Pharmacol Ther, 2018, 181: 169-182.
14. Jie Z, Liang Y, Yi P, et al. Retinoic acid regulates immune responses by promoting IL-22 and modulating S100 proteins in viral hepatitis. J Immunol, 2017, 198(9): 3448-3460.
15. Yang Z, Yan WX, Cai H, et al. S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity. J Allergy Clin Immunol, 2007, 119(1): 106-114.
16. Lin Q, Ni H, Zhong J, et al. Identification of hub genes and potential biomarkers of neutrophilic asthma: evidence from a bioinformatics analysis. J Asthma, 2023, 60(2): 348-359.
17. Yan Q, Zhang X, Xie Y , et al. Bronchial epithelial transcriptomics and experimental validation reveal asthma severity-related neutrophilc signatures and potential treatments. Commun Biol, 2024, 7(1): 181.
18. Dong N, Wang Y. MiR-30a Regulates S100A12-induced Retinal Microglial Activation and Inflammation by Targeting NLRP3. Curr Eye Res, 2019, 44(11): 1236-1243.
19. Lin K, Wang T, Tang Q, et al. IL18R1-related molecules as biomarkers for asthma severity and prognostic markers for idiopathic pulmonary fibrosis. J Proteome Res, 2023, 22(10): 3320-3331.
20. Gkavogiannakis NA, Tsoporis JN, Drosatos IA, et al. Emergent Inflammatory Markers and Echocardiographic Indices in Patients with Bronchial Asthma. Biomolecules, 2023, 13(6): 955.
21. Chen M, Ge Y, Lin W, et al. Clinical features and nasal inflammation in asthma and allergic rhinitis. Clin Exp Immunol, 2022, 208(1): 25-32.
22. Yao L, Zhao H, Tang H, et al. The receptor for advanced glycation end products is required for β-catenin stabilization in a chemical-induced asthma model. Br J Pharmacol, 2016, 173(17): 2600-2613.
23. Hofmann Bowman MA, Heydemann A, Gawdzik J, et al. Transgenic expression of human S100A12 induces structural airway abnormalities and limited lung inflammation in a mouse model of allergic inflammation. Clin Exp Allergy, 2011, 41(6): 878-889.
24. Camoretti-Mercado B, Karrar E, Nu?ez L, et al. S100A12 and the airway smooth muscle: beyond inflammation and constriction. J Allergy Ther, 2012, 3(Suppl 1): S1-007.
25. Zheng J, Dong H, Zhang T, et al. Development and validation of a novel gene signature for predicting the prognosis of idiopathic pulmonary fibrosis based on three epithelial-mesenchymal transition and immune-related genes. Front Genet, 2022, 13: 865052.
26. Zhang Z, Han N, Shen Y. S100A12 promotes inflammation and cell apoptosis in sepsis-induced ARDS via activation of NLRP3 in?ammasome signaling. Mol Immunol, 2020, 122: 38-48.
27. Kang JH, Hwang SM, Chung IY. S100A8, S100A9 and S100A12 activate airway epithelial cells to produce MUC5AC via extracellular signal-regulated kinase and nuclear factor-κB pathways. Immunology, 2015, 144(1): 79-90.
28. Kim K, Kim HJ, Binas B, et al. Inflammatory mediators ATP and S100A12 activate the NLRP3 inflammasome to induce MUC5AC production in airway epithelial cells. Biochem Biophys Res Commun, 2018, 503(2): 657-664.
29. Jiang W, Wang Z, Hu Z, et al. Blocking the ERK1/2 signal pathway can inhibit S100A12 induced human aortic smooth muscle cells damage. Cell Biol Int, 2017, 41(12): 1307-1315.
30. Mottais A, Riberi L, Falco A, et al. Epithelial-mesenchymal transition mechanisms in chronic airway diseases: a common process to target? Int J Mol Sci, 2023, 24(15): 12412.
31. Hofmann Bowman M, Wilk J, Heydemann A, et al. S100A12 mediates aortic wall remodeling and aortic aneurysm. Circ Res, 2010, 106(1): 145-154.
32. Tondera C, Laube M, Pietzsch J. Insights into binding of S100 proteins to scavenger receptors: class B scavenger receptor CD36 binds S100A12 with high affinity. Amino Acids, 2017, 49(1): 183-191.
33. Grum-Schwensen B, Klingelh?fer J, Beck M, et al. S100A4-neutralizing antibody suppresses spontaneous tumor progression, pre-metastatic niche formation and alters T-cell polarization balance. BMC Cancer, 2015, 15: 44.
34. Akirav EM, Henegariu O, Preston-Hurlburt P, et al. The receptor for advanced glycation end products (RAGE) affects T cell differentiation in OVA induced asthma. PLoS One, 2014, 9(4): e95678.
35. Mo S, Yan S, Li J, et al. S100A4 reprofiles lipid metabolism in mast cells via RAGE and PPAR-γ signaling pathway. Int Immunopharmacol, 2024, 128: 111555.
36. Liu S, Zhang H, Li Y, et al. S100A4 enhances protumor macrophage polarization by control of PPAR-γ-dependent induction of fatty acid oxidation. J Immunother Cancer, 2021, 9(6): e002548.
37. Son SE, Im DS. Activation of G p rotein-coupled estrogen receptor 1 (GPER) attenuates obesity-induced asthma by switching M1 macrophages to M2 macrophages. Int J Mol Sci, 2024, 25(17): 9532.
38. Rouleau P, Vandal K, Ryckman C, et al. The calcium-binding protein S100A12 induces neutrophil adhesion, migration, and release from bone marrow in mouse at concentrations similar to those found in human inflammatory arthritis. Clin Immunol, 2003, 107(1): 46-54.
39. Yang Y, Jiao YY, Zhang Z, et al. Neutrophil extracellular trap is an important connection between hemodialysis and acute myocardial infarction. Ren Fail, 2023, 45(1): 2216307.
40. Nishida M, Saegusa J, Tanaka S, et al. S100A12 facilitates osteoclast differentiation from human monocytes. PLoS One, 2018, 13(9): e0204140.
41. Gao J, Liu J, Lu J, et al. SKAP1 expression in cancer cells enhances colon tumor growth and impairs cytotoxic immunity by promoting neutrophil extracellular trap formation via the NFATc1/CXCL8 axis. Adv Sci (Weinh), 2024, 11(41): e2403430.
42. Quoc QL, Choi Y, Thi Bich TC, et al. S100A9 in adult asthmatic patients: a biomarker for neutrophilic asthma. Exp Mol Med, 2021, 53(7): 1170-1179.

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S100A12蛋白在哮喘中的研究進展

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