دورية أكاديمية
أعرض في EDS

Betamethasone induces potent immunosuppression and reduces HIV infection in a PBMC in vitro model.

التفاصيل البيبلوغرافية
العنوان: Betamethasone induces potent immunosuppression and reduces HIV infection in a PBMC in vitro model.
المؤلفون: Cromarty R; Mucosal Immunology Laboratory, CAPRISA, Durban, KwaZulu-Natal, South Africa., Sigal A; Africa Health Research Institute (AHRI), Durban, KwaZulu-Natal, South Africa.; Max-Planck-Institute for Infection Biology, Berlin, Germany., Liebenberg LJ; Mucosal Immunology Laboratory, CAPRISA, Durban, KwaZulu-Natal, South Africa.; Department of Medical Microbiology, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa., Mckinnon LR; Mucosal Immunology Laboratory, CAPRISA, Durban, KwaZulu-Natal, South Africa.; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, Manitoba, Canada., Abdool Karim SS; Mucosal Immunology Laboratory, CAPRISA, Durban, KwaZulu-Natal, South Africa.; Department of Epidemiology, Columbia University Mailman School of Public Health, New York, New York, USA., Passmore JS; Mucosal Immunology Laboratory, CAPRISA, Durban, KwaZulu-Natal, South Africa.; Institute of Infectious Diseases and Molecular Medicine, University of Cape Town Faculty of Health Sciences, Cape Town, Western Cape, South Africa., Archary D; Mucosal Immunology Laboratory, CAPRISA, Durban, KwaZulu-Natal, South Africa desh.archary@caprisa.org.; Department of Medical Microbiology, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa.
المصدر: Journal of investigative medicine : the official publication of the American Federation for Clinical Research [J Investig Med] 2021 Jan; Vol. 69 (1), pp. 28-40. Date of Electronic Publication: 2020 Oct 01.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: SAGE Publications Country of Publication: England NLM ID: 9501229 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1708-8267 (Electronic) Linking ISSN: 10815589 NLM ISO Abbreviation: J Investig Med Subsets: MEDLINE
أسماء مطبوعة: Publication: 2023-: [Thousand Oaks] : SAGE Publications
Original Publication: Thorofare, NJ : Slack, c1994-
مواضيع طبية MeSH: Immunosuppression Therapy*, Anti-Inflammatory Agents/*pharmacology , Betamethasone/*pharmacology , HIV/*drug effects , HIV Infections/*prevention & control, Anti-Inflammatory Agents/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Betamethasone/therapeutic use ; CD4-Positive T-Lymphocytes ; Cells, Cultured ; Disease Transmission, Infectious/prevention & control ; Female ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/transmission ; Humans ; Ibuprofen/pharmacology ; Ibuprofen/therapeutic use ; In Vitro Techniques ; Leukocytes, Mononuclear/immunology ; Phytohemagglutinins ; Toll-Like Receptors/agonists
مستخلص: Genital inflammation is an established risk factor for increased HIV acquisition risk. Certain HIV-exposed seronegative populations, who are naturally resistant to HIV infection, have an immune quiescent phenotype defined by reduced immune activation and inflammatory cytokines at the genital tract. Therefore, the aim of this study was to create an immune quiescent environment using immunomodulatory drugs to mitigate HIV infection. Using an in vitro peripheral blood mononuclear cell (PBMC) model, we found that inflammation was induced using phytohemagglutinin and Toll-like receptor (TLR) agonists Pam3CSK4 (TLR1/2), lipopolysaccharide (LPS) (TLR4) and R848 (TLR7/8). After treatment with anti-inflammatory drugs, ibuprofen (IBF) and betamethasone (BMS), PBMCs were exposed to HIV NL4-3 AD8. Multiplexed ELISA was used to measure 28 cytokines to assess inflammation. Flow cytometry was used to measure immune activation (CD38, HLA-DR and CCR5) and HIV infection (p24 production) of CD4+ T cells. BMS potently suppressed inflammation (soluble cytokines, p<0.05) and immune activation (CD4+ T cells, p<0.05). BMS significantly reduced HIV infection of CD4+ T cells only in the LPS (0.98%) and unstimulated (1.7%) conditions (p<0.02). In contrast, IBF had minimal anti-inflammatory and immunosuppressive but no anti-HIV effects. BMS demonstrated potent anti-inflammatory effects, regardless of stimulation condition. Despite uniform immunosuppression, BMS differentially affected HIV infection according to the stimulation conditions, highlighting the complex nature of these interactions. Together, these data underscore the importance of interrogating inflammatory signaling pathways to identify novel drug targets to mitigate HIV infection.
Competing Interests: Competing interests: None declared.
(© American Federation for Medical Research 2021. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)
References: AIDS. 2008 Jul 31;22(12):1493-501. (PMID: 18614873)
Mucosal Immunol. 2014 May;7(3):634-44. (PMID: 24150258)
Am J Reprod Immunol. 2016 Aug;76(2):99-107. (PMID: 26847837)
N Engl J Med. 2012 Aug 2;367(5):423-34. (PMID: 22784038)
Front Pharmacol. 2018 Sep 04;9:799. (PMID: 30233355)
Int J Biochem. 1993 Jun;25(6):845-52. (PMID: 8344441)
Mucosal Immunol. 2014 Mar;7(2):268-79. (PMID: 23801306)
FASEB J. 2012 Dec;26(12):4805-20. (PMID: 22954589)
Retrovirology. 2013 Nov 20;10:141. (PMID: 24257114)
Mucosal Immunol. 2016 Jan;9(1):194-205. (PMID: 26104913)
Mucosal Immunol. 2016 Jan;9(1):1-12. (PMID: 25872482)
Retrovirology. 2007 Jan 30;4:6. (PMID: 17263871)
N Engl J Med. 2015 Feb 5;372(6):509-18. (PMID: 25651245)
Int Rev Immunol. 2011 Feb;30(1):16-34. (PMID: 21235323)
Open Access Emerg Med. 2011 Jul 06;3:39-48. (PMID: 27147851)
Folia Biol (Praha). 2017;63(1):13-19. (PMID: 28374670)
Nat Med. 1997 Oct;3(10):1160-2. (PMID: 9334732)
AIDS Res Hum Retroviruses. 2015 Nov;31(11):1139-52. (PMID: 26204200)
AIDS. 2009 Jan 28;23(3):309-17. (PMID: 19114868)
Mol Immunol. 2005 Feb;42(2):161-82. (PMID: 15488606)
Curr HIV/AIDS Rep. 2015 Jun;12(2):216-22. (PMID: 25877253)
Sex Transm Infect. 2014 Dec;90(8):580-7. (PMID: 25107710)
N Engl J Med. 2012 Aug 2;367(5):411-22. (PMID: 22784040)
N Engl J Med. 2010 Dec 30;363(27):2587-99. (PMID: 21091279)
J Virol. 2011 Oct;85(19):10189-200. (PMID: 21813616)
J Acquir Immune Defic Syndr. 2017 Mar 1;74(3):318-325. (PMID: 28187085)
J Infect Dis. 2015 May 1;211(9):1451-60. (PMID: 25389306)
Cell Immunol. 2012 Nov;280(1):101-7. (PMID: 23298864)
J Neuroinflammation. 2013 Jul 18;10:88. (PMID: 23866773)
Nat Rev Immunol. 2017 Apr;17(4):233-247. (PMID: 28192415)
JAMA. 2012 Jul 25;308(4):353-61. (PMID: 22820788)
Cell Res. 2013 Jul;23(7):876-85. (PMID: 23732522)
J Inflamm (Lond). 2012 Jan 12;9(1):1. (PMID: 22239975)
AIDS Behav. 2015 Dec;19(12):2204-13. (PMID: 26091706)
Biochem J. 1984 Nov 15;224(1):1-12. (PMID: 6095813)
J Infect Dis. 2012 Jul 1;206(1):6-14. (PMID: 22517910)
J Control Release. 2018 May 10;277:102-113. (PMID: 29545105)
J Biol Chem. 2002 Jan 11;277(2):1509-13. (PMID: 11700329)
J Immunol. 2005 Nov 1;175(9):6117-22. (PMID: 16237108)
AIDS Res Hum Retroviruses. 2016 Jul;32(7):636-47. (PMID: 26935044)
Rheumatol Int. 2007 Apr;27(6):585-91. (PMID: 17318618)
Front Immunol. 2014 Sep 25;5:461. (PMID: 25309543)
Brain Behav Immun. 2010 Jan;24(1):19-30. (PMID: 19647070)
ISRN Obstet Gynecol. 2012;2012:673131. (PMID: 22844609)
Nat Immunol. 2015 Apr;16(4):343-53. (PMID: 25789684)
Expert Opin Drug Saf. 2016;15(4):457-65. (PMID: 26789102)
J Immunol. 2012 Nov 1;189(9):4666-73. (PMID: 22993206)
PLoS One. 2012;7(9):e45911. (PMID: 23029309)
Mucosal Immunol. 2012 May;5(3):277-87. (PMID: 22318497)
Int J Environ Res Public Health. 2013 Aug 27;10(9):3834-42. (PMID: 23985769)
Science. 1999 Nov 12;286(5443):1353-7. (PMID: 10558989)
J Acquir Immune Defic Syndr. 2012 Apr 15;59(5):427-37. (PMID: 22240463)
Cell Immunol. 2013 Nov-Dec;286(1-2):45-52. (PMID: 24321565)
J Infect Dis. 2010 Nov 1;202 Suppl 3:S339-44. (PMID: 20887221)
Retrovirology. 2011 Mar 23;8:22. (PMID: 21429204)
Immunology. 2009 Sep;128(1 Suppl):e746-57. (PMID: 19740336)
Am J Manag Care. 2013 Nov;19(14 Suppl):s267-72. (PMID: 24494609)
Immunity. 2017 Jan 17;46(1):29-37. (PMID: 28087240)
J Virol. 1995 Jun;69(6):3949-54. (PMID: 7745752)
Immunity. 2010 Mar 26;32(3):305-15. (PMID: 20346772)
Immunopharmacology. 1989 May-Jun;17(3):167-73. (PMID: 2504679)
Curr Opin HIV AIDS. 2010 Jul;5(4):305-10. (PMID: 20543605)
AIDS. 2008 Oct 1;22(15):2049-51. (PMID: 18784472)
J Steroid Biochem Mol Biol. 2000 Dec 31;75(4-5):283-90. (PMID: 11282284)
PLoS One. 2012;7(8):e43670. (PMID: 22928014)
J Cell Physiol. 2010 Nov;225(2):406-16. (PMID: 20589830)
Clin Exp Immunol. 2015 Mar;179(3):529-38. (PMID: 25354724)
Front Immunol. 2019 Jul 23;10:1705. (PMID: 31396221)
Kobe J Med Sci. 2016 Sep 9;62(4):E79-E88. (PMID: 28239073)
PLoS One. 2014 Jul 07;9(7):e101920. (PMID: 25000587)
PLoS Pathog. 2010 Apr 08;6(4):e1000852. (PMID: 20386714)
Immunol Res. 2016 Jun;64(3):765-74. (PMID: 26724942)
PLoS One. 2014 Aug 04;9(8):e104039. (PMID: 25090652)
J AIDS Clin Res. 2014 May;5(5):. (PMID: 25364618)
EMBO J. 1990 May;9(5):1551-60. (PMID: 2184033)
Annu Rev Physiol. 1989;51:683-99. (PMID: 2540703)
Clin Exp Immunol. 1999 Jan;115(1):86-90. (PMID: 9933424)
Cold Spring Harb Symp Quant Biol. 1989;54 Pt 1:1-13. (PMID: 2700931)
Clin Infect Dis. 2015 Jul 15;61(2):260-9. (PMID: 25900168)
Ann N Y Acad Sci. 2000;915:282-6. (PMID: 11193589)
Curr Protoc Cytom. 2010 Jul;Chapter 9:Unit 9.34. (PMID: 20578108)
Acta Derm Venereol. 2017 Apr 6;97(4):449-455. (PMID: 27868150)
Pain. 2008 Sep 30;139(1):15-27. (PMID: 18396374)
Indian J Dermatol. 2014 Sep;59(5):460-4. (PMID: 25284850)
Science. 2017 Jun 2;356(6341):938-945. (PMID: 28572388)
Lancet. 2016 Jan 2;387(10013):53-60. (PMID: 26364263)
Blood. 2011 Sep 22;118(12):3263-72. (PMID: 21576701)
Mol Cell Endocrinol. 2011 Mar 15;335(1):2-13. (PMID: 20398732)
Cell. 2006 Feb 24;124(4):783-801. (PMID: 16497588)
PLoS One. 2014 Jan 15;9(1):e85675. (PMID: 24454917)
J Immunol. 2012 Nov 1;189(9):4226-30. (PMID: 23024280)
Immunity. 2015 May 19;42(5):965-76. (PMID: 25992865)
Science. 2002 Apr 12;296(5566):298-300. (PMID: 11951031)
Nat Med. 2011 Jun 26;17(7):830-6. (PMID: 21706028)
Int J STD AIDS. 2005 May;16(5):392-4. (PMID: 15949075)
Immunology. 2015 Dec;146(4):557-67. (PMID: 26302175)
Endocr Rev. 1999 Aug;20(4):435-59. (PMID: 10453354)
Ann N Y Acad Sci. 2000;915:193-203. (PMID: 11193576)
Am J Prev Med. 2013 Jan;44(1 Suppl 2):S91-8. (PMID: 23253769)
Prog Allergy. 1988;44:140-52. (PMID: 3144716)
Nature. 2009 Apr 23;458(7241):1034-8. (PMID: 19262509)
PLoS One. 2015 Jun 09;10(6):e0129465. (PMID: 26057743)
J Int AIDS Soc. 2018 Jul;21(7):e25150. (PMID: 30047573)
Int Immunopharmacol. 2011 Aug;11(8):1116-9. (PMID: 21439397)
Clin Infect Dis. 2017 Jan 1;64(1):79-82. (PMID: 27694480)
N Engl J Med. 2015 Dec 3;373(23):2237-46. (PMID: 26624850)
J Virol. 2010 Nov;84(22):12082-6. (PMID: 20844049)
Curr Opin HIV AIDS. 2016 Mar;11(2):156-62. (PMID: 26628324)
Arthritis Res Ther. 2005;7(2):R370-9. (PMID: 15743485)
Front Cell Infect Microbiol. 2013 Jan 08;2:168. (PMID: 23316484)
N Engl J Med. 2012 Aug 2;367(5):399-410. (PMID: 22784037)
J Immunol. 1999 Sep 15;163(6):3524-9. (PMID: 10477627)
J Infect Dis. 2012 Oct 1;206(7):993-1001. (PMID: 22829639)
Curr HIV/AIDS Rep. 2016 Jun;13(3):158-69. (PMID: 27137200)
Br J Gen Pract. 2017 Mar;67(656):e187-e193. (PMID: 28193616)
BMC Vet Res. 2020 Mar 6;16(1):83. (PMID: 32143631)
Science. 2010 Sep 3;329(5996):1168-74. (PMID: 20643915)
Front Endocrinol (Lausanne). 2016 Apr 19;7:31. (PMID: 27148162)
Braz J Infect Dis. 2016 Mar-Apr;20(2):193-204. (PMID: 26775799)
J Immunol. 2004 Jul 1;173(1):360-6. (PMID: 15210794)
J Cell Sci. 2000 Jun;113 ( Pt 11):2085-90. (PMID: 10806119)
J Infect Dis. 2011 Nov 15;204(10):1550-6. (PMID: 21940422)
Open Microbiol J. 2008;2:49-59. (PMID: 19088911)
Am J Nephrol. 2000 Jul-Aug;20(4):291-9. (PMID: 10970982)
Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13504-9. (PMID: 9391055)
Cell Mol Life Sci. 2015 Feb;72(3):557-581. (PMID: 25332099)
J Virol. 2008 Sep;82(17):8529-36. (PMID: 18562528)
J Neuroinflammation. 2015 Dec 23;12:240. (PMID: 26700298)
Mol Cell Biol. 1995 Feb;15(2):943-53. (PMID: 7823959)
معلومات مُعتمدة: R01 AI111936 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: anti-inflammatory agents; betamethasone; glucocorticoids; immunosuppression; inflammation
المشرفين على المادة: 0 (Anti-Inflammatory Agents)
0 (Anti-Inflammatory Agents, Non-Steroidal)
0 (Phytohemagglutinins)
0 (Toll-Like Receptors)
9842X06Q6M (Betamethasone)
WK2XYI10QM (Ibuprofen)
تواريخ الأحداث: Date Created: 20201002 Date Completed: 20211109 Latest Revision: 20211204
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC7803916
DOI: 10.1136/jim-2020-001424
PMID: 33004468
قاعدة البيانات: MEDLINE
الوصف
تدمد:1708-8267
DOI:10.1136/jim-2020-001424