A BCR-ABL inhibitor GNF-2 attenuates inflammatory activation of glia and chronic pain

Gyun Jee Song, Md Habibur Rahman, Mithilesh Kumar Jha, Deepak Prasad Gupta, Sung Hee Park, Jae Hong Kim, Sun Hwa Lee, In Kyu Lee, Taebo Sim, Yong Chul Bae, Won Ha Lee, Kyoungho Suk

Research output: Contribution to journalArticle

Abstract

GNF-2 is an allosteric inhibitor of Bcr-Abl. It was developed as a new class of anti-cancer drug to treat resistant chronic myelogenous leukemia. Recent studies suggest that c-Abl inhibition would provide a neuroprotective effect in animal models of Parkinson’s disease as well as in clinical trials. However, the role of c-Abl and effects of GNF-2 in glia-mediated neuroinflammation or pain hypersensitivity has not been investigated. Thus, in the present study, we tested the hypothesis that c-Abl inhibition by GNF-2 may attenuate the inflammatory activation of glia and the ensuing pain behaviors in animal models. Our results show that GNF-2 reduced lipopolysaccharide (LPS)-induced nitric oxide and pro-inflammatory cytokine production in cultured glial cells in a c-Abl-dependent manner. The small interfering ribonucleic acid (siRNA)mediated knockdown of c-Abl attenuated LPS-induced nuclear factor kappa light chain enhancer of activated B cell (NF-κB) activation and the production of pro-inflammatory mediators in glial cell cultures. Moreover, GNF-2 administration significantly attenuated mechanical and thermal hypersensitivities in experimental models of diabetic and inflammatory pain. Together, our findings suggest the involvement of c-Abl in neuroinflammation and pain pathogenesis and that GNF-2 can be used for the management of chronic pain.

Original languageEnglish
Article number543
JournalFrontiers in Pharmacology
Volume10
Issue numberMAY
DOIs
Publication statusPublished - 2019 Jan 1

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Neuroglia
Chronic Pain
Pain
Lipopolysaccharides
Hypersensitivity
Animal Models
Neuroprotective Agents
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Parkinson Disease
Cultured Cells
Nitric Oxide
B-Lymphocytes
Theoretical Models
Cell Culture Techniques
Hot Temperature
Clinical Trials
RNA
Cytokines
Light
Pharmaceutical Preparations

Keywords

  • C-Abl
  • Glia
  • GNF-2
  • Neuroinflammation
  • Pain

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Song, G. J., Rahman, M. H., Jha, M. K., Gupta, D. P., Park, S. H., Kim, J. H., ... Suk, K. (2019). A BCR-ABL inhibitor GNF-2 attenuates inflammatory activation of glia and chronic pain. Frontiers in Pharmacology, 10(MAY), [543]. https://doi.org/10.3389/fphar.2019.00543

A BCR-ABL inhibitor GNF-2 attenuates inflammatory activation of glia and chronic pain. / Song, Gyun Jee; Rahman, Md Habibur; Jha, Mithilesh Kumar; Gupta, Deepak Prasad; Park, Sung Hee; Kim, Jae Hong; Lee, Sun Hwa; Lee, In Kyu; Sim, Taebo; Bae, Yong Chul; Lee, Won Ha; Suk, Kyoungho.

In: Frontiers in Pharmacology, Vol. 10, No. MAY, 543, 01.01.2019.

Research output: Contribution to journalArticle

Song, GJ, Rahman, MH, Jha, MK, Gupta, DP, Park, SH, Kim, JH, Lee, SH, Lee, IK, Sim, T, Bae, YC, Lee, WH & Suk, K 2019, 'A BCR-ABL inhibitor GNF-2 attenuates inflammatory activation of glia and chronic pain', Frontiers in Pharmacology, vol. 10, no. MAY, 543. https://doi.org/10.3389/fphar.2019.00543
Song, Gyun Jee ; Rahman, Md Habibur ; Jha, Mithilesh Kumar ; Gupta, Deepak Prasad ; Park, Sung Hee ; Kim, Jae Hong ; Lee, Sun Hwa ; Lee, In Kyu ; Sim, Taebo ; Bae, Yong Chul ; Lee, Won Ha ; Suk, Kyoungho. / A BCR-ABL inhibitor GNF-2 attenuates inflammatory activation of glia and chronic pain. In: Frontiers in Pharmacology. 2019 ; Vol. 10, No. MAY.
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