Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes

Loreto Carvallo, Lillie Lopez, Fa Yun Che, Jihyeon Lim, Eliseo Eugenin, Dionna W. Williams, Edward Nieves, Tina M. Calderon, Carlos Madrid-Aliste, Andras Fiser, Louis Weiss, Ruth Hogue Angeletti, Joan W. Berman

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Despite successful combined antiretroviral therapy, ∼60% of HIV-infected people exhibit HIV-associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV-infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9 were identified and had not been shown previously to be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction.

Original languageEnglish (US)
Pages (from-to)3246-3258
Number of pages13
JournalJournal of Immunology
Volume194
Issue number7
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

Fingerprint

Buprenorphine
Monocytes
HIV
Phosphorylation
Opiate Alkaloids
CD43 Antigens
CCR2 Receptors
Ala(2)-MePhe(4)-Gly(5)-enkephalin
Opioid-Related Disorders
Opioid Receptors
p38 Mitogen-Activated Protein Kinases
Chemotaxis
Proteomics
Proteins
Therapeutics
Cell Membrane
Phenotype

ASJC Scopus subject areas

  • Immunology

Cite this

Carvallo, L., Lopez, L., Che, F. Y., Lim, J., Eugenin, E., Williams, D. W., ... Berman, J. W. (2015). Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes. Journal of Immunology, 194(7), 3246-3258. https://doi.org/10.4049/jimmunol.1302647

Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes. / Carvallo, Loreto; Lopez, Lillie; Che, Fa Yun; Lim, Jihyeon; Eugenin, Eliseo; Williams, Dionna W.; Nieves, Edward; Calderon, Tina M.; Madrid-Aliste, Carlos; Fiser, Andras; Weiss, Louis; Angeletti, Ruth Hogue; Berman, Joan W.

In: Journal of Immunology, Vol. 194, No. 7, 01.04.2015, p. 3246-3258.

Research output: Contribution to journalArticle

Carvallo, L, Lopez, L, Che, FY, Lim, J, Eugenin, E, Williams, DW, Nieves, E, Calderon, TM, Madrid-Aliste, C, Fiser, A, Weiss, L, Angeletti, RH & Berman, JW 2015, 'Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes', Journal of Immunology, vol. 194, no. 7, pp. 3246-3258. https://doi.org/10.4049/jimmunol.1302647
Carvallo, Loreto ; Lopez, Lillie ; Che, Fa Yun ; Lim, Jihyeon ; Eugenin, Eliseo ; Williams, Dionna W. ; Nieves, Edward ; Calderon, Tina M. ; Madrid-Aliste, Carlos ; Fiser, Andras ; Weiss, Louis ; Angeletti, Ruth Hogue ; Berman, Joan W. / Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes. In: Journal of Immunology. 2015 ; Vol. 194, No. 7. pp. 3246-3258.
@article{f3e81a10d868466ebb2b884a4af530ad,
title = "Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes",
abstract = "Despite successful combined antiretroviral therapy, ∼60{\%} of HIV-infected people exhibit HIV-associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV-infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9 were identified and had not been shown previously to be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction.",
author = "Loreto Carvallo and Lillie Lopez and Che, {Fa Yun} and Jihyeon Lim and Eliseo Eugenin and Williams, {Dionna W.} and Edward Nieves and Calderon, {Tina M.} and Carlos Madrid-Aliste and Andras Fiser and Louis Weiss and Angeletti, {Ruth Hogue} and Berman, {Joan W.}",
year = "2015",
month = "4",
day = "1",
doi = "10.4049/jimmunol.1302647",
language = "English (US)",
volume = "194",
pages = "3246--3258",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "7",

}

TY - JOUR

T1 - Buprenorphine decreases the CCL2-mediated chemotactic response of monocytes

AU - Carvallo, Loreto

AU - Lopez, Lillie

AU - Che, Fa Yun

AU - Lim, Jihyeon

AU - Eugenin, Eliseo

AU - Williams, Dionna W.

AU - Nieves, Edward

AU - Calderon, Tina M.

AU - Madrid-Aliste, Carlos

AU - Fiser, Andras

AU - Weiss, Louis

AU - Angeletti, Ruth Hogue

AU - Berman, Joan W.

PY - 2015/4/1

Y1 - 2015/4/1

N2 - Despite successful combined antiretroviral therapy, ∼60% of HIV-infected people exhibit HIV-associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV-infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9 were identified and had not been shown previously to be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction.

AB - Despite successful combined antiretroviral therapy, ∼60% of HIV-infected people exhibit HIV-associated neurocognitive disorders (HAND). CCL2 is elevated in the CNS of infected people with HAND and mediates monocyte influx into the CNS, which is critical in neuroAIDS. Many HIV-infected opiate abusers have increased neuroinflammation that may augment HAND. Buprenorphine is used to treat opiate addiction. However, there are few studies that examine its impact on HIV neuropathogenesis. We show that buprenorphine reduces the chemotactic phenotype of monocytes. Buprenorphine decreases the formation of membrane projections in response to CCL2. It also decreases CCL2-induced chemotaxis and mediates a delay in reinsertion of the CCL2 receptor, CCR2, into the cell membrane after CCL2-mediated receptor internalization, suggesting a mechanism of action of buprenorphine. Signaling pathways in CCL2-induced migration include increased phosphorylation of p38 MAPK and of the junctional protein JAM-A. We show that buprenorphine decreases these phosphorylations in CCL2-treated monocytes. Using DAMGO, CTAP, and Nor-BNI, we demonstrate that the effect of buprenorphine on CCL2 signaling is opioid receptor mediated. To identify additional potential mechanisms by which buprenorphine inhibits CCL2-induced monocyte migration, we performed proteomic analyses to characterize additional proteins in monocytes whose phosphorylation after CCL2 treatment was inhibited by buprenorphine. Leukosialin and S100A9 were identified and had not been shown previously to be involved in monocyte migration. We propose that buprenorphine limits CCL2-mediated monocyte transmigration into the CNS, thereby reducing neuroinflammation characteristic of HAND. Our findings underscore the use of buprenorphine as a therapeutic for neuroinflammation as well as for addiction.

UR - http://www.scopus.com/inward/record.url?scp=84925862733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84925862733&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.1302647

DO - 10.4049/jimmunol.1302647

M3 - Article

VL - 194

SP - 3246

EP - 3258

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 7

ER -