Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients

Amena W. Smith; Bently P. Doonan; William R. Tyor; Nada Abou-Fayssal; Azizul Haque; Naren L. Banik

doi:10.1016/j.jneuroim.2010.09.030

Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients

Amena W. Smith, Bently P. Doonan, William R. Tyor, Nada Abou-Fayssal, Azizul Haque, Naren L. Banik

Research output: Contribution to journal › Article › peer-review

32 Scopus citations

Abstract

Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin-specific T cells into the central nervous system (CNS). During active disease, pro-inflammatory Th1/Th17 cells predominate over immunoregulatory Th2/Treg cells. Here, we show that calpain inhibition downregulates Th1/Th17 inflammatory cytokines and mRNA in MS patient peripheral blood mononuclear cells (PBMCs) activated with anti-CD3/28 or MBP. Interestingly, calpain inhibition elevated IDO gene expression in MS PBMCs, which was markedly decreased in calpain expressing cells. Functional assay showed that incubation of MS patient PBMCs with calpain inhibitor or recombinant IDO attenuates T cell proliferation. These results suggest that calpain inhibition may attenuate MS pathology and augment the efficacy of standard immunomodulatory agents used to treat this disease.

Original language	English
Pages (from-to)	179-185
Number of pages	7
Journal	Journal of Neuroimmunology
Volume	232
Issue number	1-2
DOIs	https://doi.org/10.1016/j.jneuroim.2010.09.030
State	Published - Mar 2011
Externally published	Yes

Keywords

Calpain
Indoleamine 2, 3-dioxygenase
Multiple sclerosis
Peripheral blood mononuclear cells
Th17

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10.1016/j.jneuroim.2010.09.030

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@article{b65c997d7539419c921124201af30ada,

title = "Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients",

abstract = "Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin-specific T cells into the central nervous system (CNS). During active disease, pro-inflammatory Th1/Th17 cells predominate over immunoregulatory Th2/Treg cells. Here, we show that calpain inhibition downregulates Th1/Th17 inflammatory cytokines and mRNA in MS patient peripheral blood mononuclear cells (PBMCs) activated with anti-CD3/28 or MBP. Interestingly, calpain inhibition elevated IDO gene expression in MS PBMCs, which was markedly decreased in calpain expressing cells. Functional assay showed that incubation of MS patient PBMCs with calpain inhibitor or recombinant IDO attenuates T cell proliferation. These results suggest that calpain inhibition may attenuate MS pathology and augment the efficacy of standard immunomodulatory agents used to treat this disease.",

keywords = "Calpain, Indoleamine 2, 3-dioxygenase, Multiple sclerosis, Peripheral blood mononuclear cells, Th17",

author = "Smith, {Amena W.} and Doonan, {Bently P.} and Tyor, {William R.} and Nada Abou-Fayssal and Azizul Haque and Banik, {Naren L.}",

note = "Funding Information: This work has been supported by grants ( 5R01NS041088 , 5R01NS056176 , 5R01NS065456 , and CA129560 ) from the National Institutes of Health (NIH) , grant # 3024 from the Leukemia and Lymphoma Society and the MUSC Hollings Cancer Center .",

year = "2011",

month = mar,

doi = "10.1016/j.jneuroim.2010.09.030",

language = "English",

volume = "232",

pages = "179--185",

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T1 - Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients

AU - Smith, Amena W.

AU - Doonan, Bently P.

AU - Tyor, William R.

AU - Abou-Fayssal, Nada

AU - Haque, Azizul

AU - Banik, Naren L.

N1 - Funding Information: This work has been supported by grants ( 5R01NS041088 , 5R01NS056176 , 5R01NS065456 , and CA129560 ) from the National Institutes of Health (NIH) , grant # 3024 from the Leukemia and Lymphoma Society and the MUSC Hollings Cancer Center .

PY - 2011/3

Y1 - 2011/3

N2 - Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin-specific T cells into the central nervous system (CNS). During active disease, pro-inflammatory Th1/Th17 cells predominate over immunoregulatory Th2/Treg cells. Here, we show that calpain inhibition downregulates Th1/Th17 inflammatory cytokines and mRNA in MS patient peripheral blood mononuclear cells (PBMCs) activated with anti-CD3/28 or MBP. Interestingly, calpain inhibition elevated IDO gene expression in MS PBMCs, which was markedly decreased in calpain expressing cells. Functional assay showed that incubation of MS patient PBMCs with calpain inhibitor or recombinant IDO attenuates T cell proliferation. These results suggest that calpain inhibition may attenuate MS pathology and augment the efficacy of standard immunomodulatory agents used to treat this disease.

AB - Multiple sclerosis (MS) pathology is marked by the massive infiltration of myelin-specific T cells into the central nervous system (CNS). During active disease, pro-inflammatory Th1/Th17 cells predominate over immunoregulatory Th2/Treg cells. Here, we show that calpain inhibition downregulates Th1/Th17 inflammatory cytokines and mRNA in MS patient peripheral blood mononuclear cells (PBMCs) activated with anti-CD3/28 or MBP. Interestingly, calpain inhibition elevated IDO gene expression in MS PBMCs, which was markedly decreased in calpain expressing cells. Functional assay showed that incubation of MS patient PBMCs with calpain inhibitor or recombinant IDO attenuates T cell proliferation. These results suggest that calpain inhibition may attenuate MS pathology and augment the efficacy of standard immunomodulatory agents used to treat this disease.

KW - Calpain

KW - Indoleamine 2, 3-dioxygenase

KW - Multiple sclerosis

KW - Peripheral blood mononuclear cells

KW - Th17

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SN - 0165-5728

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JF - Journal of Neuroimmunology

IS - 1-2

ER -

Regulation of Th1/Th17 cytokines and IDO gene expression by inhibition of calpain in PBMCs from MS patients

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Keywords

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