CXCL9、CXCL10在肺动脉高压中的研究进展_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

李汝芳 ,  李登媛

云南省第一人民医院呼吸与危重症医学科（云南昆明 650100）;

Corresponding author：

李登媛, Email: lidengyuan111@126.com

Keywords：

DOI：

10.7507/1671-6205.202403027

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Citation： 李汝芳, 李登媛. CXCL9、CXCL10在肺动脉高压中的研究进展. Chinese Journal of Respiratory and Critical Care Medicine, 2024, 23(11): 818-822. doi: 10.7507/1671-6205.202403027 Copy

1.	Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol, 2004, 43(12 Suppl S): 13s-24s.
2.	Boucly A, Savale L, Jaïs X, et al. Association between initial treatment strategy and long-term survival in pulmonary arterial hypertension. Am J Respir Crit Care Med, 2021, 204(7): 842-854.
3.	Sitbon O, Humbert M, Jaïs X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation, 2005, 111(23): 3105-3111.
4.	Montani D, Chaumais MC, Guignabert C, et al. Targeted therapies in pulmonary arterial hypertension. Pharmacol Ther, 2014, 141(2): 172-191.
5.	Humbert M, Lau EM, Montani D, et al. Advances in therapeutic interventions for patients with pulmonary arterial hypertension. Circulation, 2014, 130(24): 2189-2208.
6.	Farber HW, Miller DP, Poms AD, et al. Five-year outcomes of patients enrolled in the REVEAL Registry. Chest, 2015, 148(4): 1043-1954.
7.	Perros F, Dorfmüller P, Souza R, et al. Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension. Eur Respir J, 2007, 29(5): 937-943.
8.	Hassoun PM, Mouthon L, Barberà JA, et al. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol, 2009, 54(1 Suppl): S10-S19.
9.	Tuder RM, Groves B, Badesch DB, et al. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol, 1994, 144(2): 275-285.
10.	Dorfmüller P, Humbert M, Perros F, et al. Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol, 2007, 38(6): 893-902.
11.	El Chami H, Hassoun PM. Immune and inflammatory mechanisms in pulmonary arterial hypertension. Prog Cardiovasc Dis, 2012, 55(2): 218-228.
12.	Li C, Liu P, Song R, et al. Immune cells and autoantibodies in pulmonary arterial hypertension. Acta Biochim Biophys Sin (Shanghai), 2017, 49(12): 1047-1057.
13.	Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity, 2000, 12(2): 121-127.
14.	Hughes CE, Nibbs RJB. A guide to chemokines and their receptors. Febs J, 2018, 285(16): 2944-2971.
15.	Romagnani P, Lasagni L, Annunziato F, et al. CXC chemokines: the regulatory link between inflammation and angiogenesis. Trends Immunol, 2004, 25(4): 201-209.
16.	Lasagni L, Francalanci M, Annunziato F, et al. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med, 2003, 197(11): 1537-1549.
17.	Wu T, Yang W, Sun A, et al. The role of CXC chemokines in cancer progression. Cancers (Basel), 2022, 15(1): 167.
18.	Ridiandries A, Tan JT, Bursill CA. The role of CC-Chemokines in the regulation of angiogenesis. Int J Mol Sci, 2016, 17(11): 1856.
19.	Komolafe K, Pacurari M. CXC Chemokines in the pathogenesis of pulmonary disease and pharmacological relevance. Int J Inflam, 2022, 2022: 4558159.
20.	杨罡, 赵峻, 张云辉. CXC型趋化因子及其受体轴在慢性阻塞性肺疾病中的研究进展. 中国呼吸与危重监护杂志, 2021, 20(10): 748-752.
21.	Wu K, Yu S, Liu Q, et al. The clinical significance of CXCL5 in non-small cell lung cancer. Onco Targets Ther, 2017, 10: 5561-5573.
22.	Zhou C, Gao Y, Ding P, et al. The role of CXCL family members in different diseases. Cell Death Discov, 2023, 9(1): 212.
23.	White GE, Iqbal AJ, Greaves DR. CC chemokine receptors and chronic inflammation--therapeutic opportunities and pharmacological challenges. Pharmacol Rev, 2013, 65(1): 47-89.
24.	Sanchez O, Marcos E, Perros F, et al. Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med, 2007, 176(10): 1041-1047.
25.	Mamazhakypov A, Viswanathan G, Lawrie A, et al. The role of chemokines and chemokine receptors in pulmonary arterial hypertension. Br J Pharmacol, 2021, 178(1): 72-89.
26.	Li Z, Jiang J, Gao S. Potential of C-X-C motif chemokine ligand 1/8/10/12 as diagnostic and prognostic biomarkers in idiopathic pulmonary arterial hypertension. Clin Respir J, 2021, 15(12): 1302-1309.
27.	Olsson KM, Olle S, Fuge J, et al. CXCL13 in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Respir Res, 2016, 17: 21.
28.	van Bon L, Affandi AJ, Broen J, et al. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N Engl J Med, 2014, 370(5): 433-443.
29.	Yang T, Li ZN, Chen G, et al. Increased levels of plasma CXC-Chemokine Ligand 10, 12 and 16 are associated with right ventricular function in patients with idiopathic pulmonary arterial hypertension. Heart Lung, 2014, 43(4): 322-327.
30.	Luster AD, Ravetch JV. Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med, 1987, 166(4): 1084-1097.
31.	Lacalle RA, Blanco R, Carmona-Rodríguez L, et al. Chemokine receptor signaling and the hallmarks of cancer. Int Rev Cell Mol Biol, 2017, 331: 181-244.
32.	Ding Q, Lu P, Xia Y, et al. CXCL9: evidence and contradictions for its role in tumor progression. Cancer Med, 2016, 5(11): 3246-3259.
33.	Van Raemdonck K, Van den Steen PE, Liekens S, et al. CXCR3 ligands in disease and therapy. Cytokine Growth Factor Rev, 2015, 26(3): 311-327.
34.	Bachelerie F, Ben-Baruch A, Burkhardt AM, et al. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev, 2014, 66(1): 1-79.
35.	Zohar Y, Wildbaum G, Novak R, et al. CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis. J Clin Invest, 2014, 124(5): 2009-2022.
36.	George PM, Oliver E, Dorfmuller P, et al. Evidence for the involvement of type I interferon in pulmonary arterial hypertension. Circ Res, 2014, 114(4): 677-688.
37.	Badiger R, Mitchell JA, Gashaw H, et al. Effect of different interferonα2 preparations on IP10 and ET-1 release from human lung cells. PLoS One, 2012, 7(10): e46779.
38.	Costa J, Zhu Y, Cox T, et al. Inflammatory response of pulmonary artery smooth muscle cells exposed to oxidative and biophysical stress. Inflammation, 2018, 41(4): 1250-1258.
39.	Farkas D, Thompson AAR, Bhagwani AR, et al. Toll-like receptor 3 is a therapeutic target for pulmonary hypertension. Am J Respir Crit Care Med, 2019, 199(2): 199-210.
40.	Ross DJ, Strieter RM, Fishbein MC, et al. Type I immune response cytokine-chemokine cascade is associated with pulmonary arterial hypertension. J Heart Lung Transplant, 2012, 31(8): 865-873.
41.	Koudstaal T, van Uden D, van Hulst JAC, et al. Plasma markers in pulmonary hypertension subgroups correlate with patient survival. Respir Res, 2021, 22(1): 137.
42.	Dong H, Li X, Cai M, et al. Integrated bioinformatic analysis reveals the underlying molecular mechanism of and potential drugs for pulmonary arterial hypertension. Aging (Albany NY), 2021, 13(10): 14234-14257.
43.	Boucly A, Tu L, Guignabert C, et al. Cytokines as prognostic biomarkers in pulmonary arterial hypertension. Eur Respir J, 2023, 61(3): 2201232.
44.	Cunningham CM, Li M, Ruffenach G, et al. Y-chromosome gene, Uty, protects against pulmonary hypertension by reducing proinflammatory chemokines. Am J Respir Crit Care Med, 2022, 206(2): 186-196.
45.	Heresi GA, Aytekin M, Newman J, et al. CXC-chemokine ligand 10 in idiopathic pulmonary arterial hypertension: marker of improved survival. Lung, 2010, 188(3): 191-197.
46.	Masri FA, Anand-Apte B, Vasanji A, et al. Definitive evidence of fundamental and inherent alteration in the phenotype of primary pulmonary hypertension endothelial cells in angiogenesis. Chest, 2005, 128(6 Suppl): 571s.
47.	Darakhshan S, Hassanshahi G, Mofidifar Z, et al. CXCL9/CXCL10 angiostasis CXC-chemokines in parallel with the CXCL12 as an angiogenesis CXC-chemokine are variously expressed in pre-eclamptic-women and their neonates. Pregnancy Hypertens, 2019, 17: 36-42.
48.	Strieter RM, Burdick MD, Gomperts BN, et al. CXC chemokines in angiogenesis. Cytokine Growth Factor Rev, 2005, 16(6): 593-609.
49.	Bodnar RJ, Yates CC, Wells A. IP-10 blocks vascular endothelial growth factor-induced endothelial cell motility and tube formation via inhibition of calpain. Circ Res, 2006, 98(5): 617-625.
50.	Huynh RH, Saggar R, Li N, et al. Elevated baseline concentrations of Cxcl-9 and-10 are associated with irreversible vascular remodeling of the pulmonary circulation in portopulmonary hypertension. American Thoracic Society, 2017, A4230-A4230.
51.	Hirsch K, Nolley S, Ralph DD, et al. Circulating markers of inflammation and angiogenesis and clinical outcomes across subtypes of pulmonary arterial hypertension. J Heart Lung Transplant, 2023, 42(2): 173-182.
52.	Evans CE, Cober ND, Dai Z, et al. Endothelial cells in the pathogenesis of pulmonary arterial hypertension. Eur Respir J, 2021, 58(3): 2003957.
53.	Kurakula K, Smolders V, Tura-Ceide O, et al. Endothelial dysfunction in pulmonary hypertension: cause or consequence? Biomedicines, 2021, 9(1): 57.

1. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol, 2004, 43(12 Suppl S): 13s-24s.
2. Boucly A, Savale L, Jaïs X, et al. Association between initial treatment strategy and long-term survival in pulmonary arterial hypertension. Am J Respir Crit Care Med, 2021, 204(7): 842-854.
3. Sitbon O, Humbert M, Jaïs X, et al. Long-term response to calcium channel blockers in idiopathic pulmonary arterial hypertension. Circulation, 2005, 111(23): 3105-3111.
4. Montani D, Chaumais MC, Guignabert C, et al. Targeted therapies in pulmonary arterial hypertension. Pharmacol Ther, 2014, 141(2): 172-191.
5. Humbert M, Lau EM, Montani D, et al. Advances in therapeutic interventions for patients with pulmonary arterial hypertension. Circulation, 2014, 130(24): 2189-2208.
6. Farber HW, Miller DP, Poms AD, et al. Five-year outcomes of patients enrolled in the REVEAL Registry. Chest, 2015, 148(4): 1043-1954.
7. Perros F, Dorfmüller P, Souza R, et al. Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension. Eur Respir J, 2007, 29(5): 937-943.
8. Hassoun PM, Mouthon L, Barberà JA, et al. Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol, 2009, 54(1 Suppl): S10-S19.
9. Tuder RM, Groves B, Badesch DB, et al. Exuberant endothelial cell growth and elements of inflammation are present in plexiform lesions of pulmonary hypertension. Am J Pathol, 1994, 144(2): 275-285.
10. Dorfmüller P, Humbert M, Perros F, et al. Fibrous remodeling of the pulmonary venous system in pulmonary arterial hypertension associated with connective tissue diseases. Hum Pathol, 2007, 38(6): 893-902.
11. El Chami H, Hassoun PM. Immune and inflammatory mechanisms in pulmonary arterial hypertension. Prog Cardiovasc Dis, 2012, 55(2): 218-228.
12. Li C, Liu P, Song R, et al. Immune cells and autoantibodies in pulmonary arterial hypertension. Acta Biochim Biophys Sin (Shanghai), 2017, 49(12): 1047-1057.
13. Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity, 2000, 12(2): 121-127.
14. Hughes CE, Nibbs RJB. A guide to chemokines and their receptors. Febs J, 2018, 285(16): 2944-2971.
15. Romagnani P, Lasagni L, Annunziato F, et al. CXC chemokines: the regulatory link between inflammation and angiogenesis. Trends Immunol, 2004, 25(4): 201-209.
16. Lasagni L, Francalanci M, Annunziato F, et al. An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4. J Exp Med, 2003, 197(11): 1537-1549.
17. Wu T, Yang W, Sun A, et al. The role of CXC chemokines in cancer progression. Cancers (Basel), 2022, 15(1): 167.
18. Ridiandries A, Tan JT, Bursill CA. The role of CC-Chemokines in the regulation of angiogenesis. Int J Mol Sci, 2016, 17(11): 1856.
19. Komolafe K, Pacurari M. CXC Chemokines in the pathogenesis of pulmonary disease and pharmacological relevance. Int J Inflam, 2022, 2022: 4558159.
20. 杨罡, 赵峻, 张云辉. CXC型趋化因子及其受体轴在慢性阻塞性肺疾病中的研究进展. 中国呼吸与危重监护杂志, 2021, 20(10): 748-752.
21. Wu K, Yu S, Liu Q, et al. The clinical significance of CXCL5 in non-small cell lung cancer. Onco Targets Ther, 2017, 10: 5561-5573.
22. Zhou C, Gao Y, Ding P, et al. The role of CXCL family members in different diseases. Cell Death Discov, 2023, 9(1): 212.
23. White GE, Iqbal AJ, Greaves DR. CC chemokine receptors and chronic inflammation--therapeutic opportunities and pharmacological challenges. Pharmacol Rev, 2013, 65(1): 47-89.
24. Sanchez O, Marcos E, Perros F, et al. Role of endothelium-derived CC chemokine ligand 2 in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med, 2007, 176(10): 1041-1047.
25. Mamazhakypov A, Viswanathan G, Lawrie A, et al. The role of chemokines and chemokine receptors in pulmonary arterial hypertension. Br J Pharmacol, 2021, 178(1): 72-89.
26. Li Z, Jiang J, Gao S. Potential of C-X-C motif chemokine ligand 1/8/10/12 as diagnostic and prognostic biomarkers in idiopathic pulmonary arterial hypertension. Clin Respir J, 2021, 15(12): 1302-1309.
27. Olsson KM, Olle S, Fuge J, et al. CXCL13 in idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Respir Res, 2016, 17: 21.
28. van Bon L, Affandi AJ, Broen J, et al. Proteome-wide analysis and CXCL4 as a biomarker in systemic sclerosis. N Engl J Med, 2014, 370(5): 433-443.
29. Yang T, Li ZN, Chen G, et al. Increased levels of plasma CXC-Chemokine Ligand 10, 12 and 16 are associated with right ventricular function in patients with idiopathic pulmonary arterial hypertension. Heart Lung, 2014, 43(4): 322-327.
30. Luster AD, Ravetch JV. Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med, 1987, 166(4): 1084-1097.
31. Lacalle RA, Blanco R, Carmona-Rodríguez L, et al. Chemokine receptor signaling and the hallmarks of cancer. Int Rev Cell Mol Biol, 2017, 331: 181-244.
32. Ding Q, Lu P, Xia Y, et al. CXCL9: evidence and contradictions for its role in tumor progression. Cancer Med, 2016, 5(11): 3246-3259.
33. Van Raemdonck K, Van den Steen PE, Liekens S, et al. CXCR3 ligands in disease and therapy. Cytokine Growth Factor Rev, 2015, 26(3): 311-327.
34. Bachelerie F, Ben-Baruch A, Burkhardt AM, et al. International Union of Basic and Clinical Pharmacology. [corrected]. LXXXIX. Update on the extended family of chemokine receptors and introducing a new nomenclature for atypical chemokine receptors. Pharmacol Rev, 2014, 66(1): 1-79.
35. Zohar Y, Wildbaum G, Novak R, et al. CXCL11-dependent induction of FOXP3-negative regulatory T cells suppresses autoimmune encephalomyelitis. J Clin Invest, 2014, 124(5): 2009-2022.
36. George PM, Oliver E, Dorfmuller P, et al. Evidence for the involvement of type I interferon in pulmonary arterial hypertension. Circ Res, 2014, 114(4): 677-688.
37. Badiger R, Mitchell JA, Gashaw H, et al. Effect of different interferonα2 preparations on IP10 and ET-1 release from human lung cells. PLoS One, 2012, 7(10): e46779.
38. Costa J, Zhu Y, Cox T, et al. Inflammatory response of pulmonary artery smooth muscle cells exposed to oxidative and biophysical stress. Inflammation, 2018, 41(4): 1250-1258.
39. Farkas D, Thompson AAR, Bhagwani AR, et al. Toll-like receptor 3 is a therapeutic target for pulmonary hypertension. Am J Respir Crit Care Med, 2019, 199(2): 199-210.
40. Ross DJ, Strieter RM, Fishbein MC, et al. Type I immune response cytokine-chemokine cascade is associated with pulmonary arterial hypertension. J Heart Lung Transplant, 2012, 31(8): 865-873.
41. Koudstaal T, van Uden D, van Hulst JAC, et al. Plasma markers in pulmonary hypertension subgroups correlate with patient survival. Respir Res, 2021, 22(1): 137.
42. Dong H, Li X, Cai M, et al. Integrated bioinformatic analysis reveals the underlying molecular mechanism of and potential drugs for pulmonary arterial hypertension. Aging (Albany NY), 2021, 13(10): 14234-14257.
43. Boucly A, Tu L, Guignabert C, et al. Cytokines as prognostic biomarkers in pulmonary arterial hypertension. Eur Respir J, 2023, 61(3): 2201232.
44. Cunningham CM, Li M, Ruffenach G, et al. Y-chromosome gene, Uty, protects against pulmonary hypertension by reducing proinflammatory chemokines. Am J Respir Crit Care Med, 2022, 206(2): 186-196.
45. Heresi GA, Aytekin M, Newman J, et al. CXC-chemokine ligand 10 in idiopathic pulmonary arterial hypertension: marker of improved survival. Lung, 2010, 188(3): 191-197.
46. Masri FA, Anand-Apte B, Vasanji A, et al. Definitive evidence of fundamental and inherent alteration in the phenotype of primary pulmonary hypertension endothelial cells in angiogenesis. Chest, 2005, 128(6 Suppl): 571s.
47. Darakhshan S, Hassanshahi G, Mofidifar Z, et al. CXCL9/CXCL10 angiostasis CXC-chemokines in parallel with the CXCL12 as an angiogenesis CXC-chemokine are variously expressed in pre-eclamptic-women and their neonates. Pregnancy Hypertens, 2019, 17: 36-42.
48. Strieter RM, Burdick MD, Gomperts BN, et al. CXC chemokines in angiogenesis. Cytokine Growth Factor Rev, 2005, 16(6): 593-609.
49. Bodnar RJ, Yates CC, Wells A. IP-10 blocks vascular endothelial growth factor-induced endothelial cell motility and tube formation via inhibition of calpain. Circ Res, 2006, 98(5): 617-625.
50. Huynh RH, Saggar R, Li N, et al. Elevated baseline concentrations of Cxcl-9 and-10 are associated with irreversible vascular remodeling of the pulmonary circulation in portopulmonary hypertension. American Thoracic Society, 2017, A4230-A4230.
51. Hirsch K, Nolley S, Ralph DD, et al. Circulating markers of inflammation and angiogenesis and clinical outcomes across subtypes of pulmonary arterial hypertension. J Heart Lung Transplant, 2023, 42(2): 173-182.
52. Evans CE, Cober ND, Dai Z, et al. Endothelial cells in the pathogenesis of pulmonary arterial hypertension. Eur Respir J, 2021, 58(3): 2003957.
53. Kurakula K, Smolders V, Tura-Ceide O, et al. Endothelial dysfunction in pulmonary hypertension: cause or consequence? Biomedicines, 2021, 9(1): 57.

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CXCL9、CXCL10在肺动脉高压中的研究进展

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