Nerve growth factor: A key local regulator in the pathogenesis of inflammatory arthritis

Siba P Raychaudhuri, Smriti K. Raychaudhuri, Kondala R. Atkuri, Leonard A. Herzenberg, Leonore A. Herzenberg

Research output: Contribution to journalArticle

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Abstract

Objective The effect of nerve growth factor (NGF) and its receptor (NGFR) in inflammatory diseases is a novel research field. The purpose of this study was to investigate the role of NGF/NGFR in human T cell subpopulations and fibroblast-like synovial cells (FLS) and examine its pathophysiologic significance in psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Methods Expression of NGF/NGFR was examined in synovial fluid (SF), FLS, peripheral blood (PB)-derived T cells, and SF-derived T cells from patients with PsA, RA, and osteoarthritis (OA). NGF levels were determined by enzyme-linked immunosorbent assay. NGF-induced T cell/FLS proliferation was examined by MTT assay. Low-affinity (p75)/high-affinity (TrkA) NGFR expression was determined by high-dimensional fluorescence-activated cell sorting. A monochlorobimane assay was used to determine the effect of NGF on T cell survival. Results Levels of NGF were higher in SF samples from PsA and RA patients as compared to SF samples from OA patients. NGF-induced FLS proliferation was more marked in PsA and RA patients. TrkA was up-regulated on activated SF T cells from PsA (mean ± SD 22 ± 6.2%) and RA (8 ± 1.3%) patients, whereas in SF samples from OA patients, TrkA+CD3+ T cells were not detectable. NGF induced the proliferation of PB T cells, induced the phosphorylation of Akt in activated T cells, and consistent with known pAkt activity, inhibited tumor necrosis factor α-induced cell death in these T cells. Conclusion Based on our findings, we propose a model in which NGF secreted by FLS into PsA and RA synovium promotes the survival of activated autoreactive T cells as well as FLS proliferation. Thus, NGF has the potential to sustain the chronic inflammatory cascades of arthritis of autoimmune origin.

Original languageEnglish (US)
Pages (from-to)3243-3252
Number of pages10
JournalArthritis and Rheumatism
Volume63
Issue number11
DOIs
StatePublished - Nov 2011

Fingerprint

Nerve Growth Factor
Arthritis
Psoriatic Arthritis
T-Lymphocytes
Synovial Fluid
Nerve Growth Factor Receptor
Rheumatoid Arthritis
Fibroblasts
Osteoarthritis
Cell Proliferation
Blood Cells
Synovial Membrane
Cell Survival
Flow Cytometry
Cell Death
Tumor Necrosis Factor-alpha
Enzyme-Linked Immunosorbent Assay
Phosphorylation
Survival

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Rheumatology
  • Pharmacology (medical)

Cite this

Nerve growth factor : A key local regulator in the pathogenesis of inflammatory arthritis. / Raychaudhuri, Siba P; Raychaudhuri, Smriti K.; Atkuri, Kondala R.; Herzenberg, Leonard A.; Herzenberg, Leonore A.

In: Arthritis and Rheumatism, Vol. 63, No. 11, 11.2011, p. 3243-3252.

Research output: Contribution to journalArticle

Raychaudhuri, SP, Raychaudhuri, SK, Atkuri, KR, Herzenberg, LA & Herzenberg, LA 2011, 'Nerve growth factor: A key local regulator in the pathogenesis of inflammatory arthritis', Arthritis and Rheumatism, vol. 63, no. 11, pp. 3243-3252. https://doi.org/10.1002/art.30564
Raychaudhuri, Siba P ; Raychaudhuri, Smriti K. ; Atkuri, Kondala R. ; Herzenberg, Leonard A. ; Herzenberg, Leonore A. / Nerve growth factor : A key local regulator in the pathogenesis of inflammatory arthritis. In: Arthritis and Rheumatism. 2011 ; Vol. 63, No. 11. pp. 3243-3252.
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abstract = "Objective The effect of nerve growth factor (NGF) and its receptor (NGFR) in inflammatory diseases is a novel research field. The purpose of this study was to investigate the role of NGF/NGFR in human T cell subpopulations and fibroblast-like synovial cells (FLS) and examine its pathophysiologic significance in psoriatic arthritis (PsA) and rheumatoid arthritis (RA). Methods Expression of NGF/NGFR was examined in synovial fluid (SF), FLS, peripheral blood (PB)-derived T cells, and SF-derived T cells from patients with PsA, RA, and osteoarthritis (OA). NGF levels were determined by enzyme-linked immunosorbent assay. NGF-induced T cell/FLS proliferation was examined by MTT assay. Low-affinity (p75)/high-affinity (TrkA) NGFR expression was determined by high-dimensional fluorescence-activated cell sorting. A monochlorobimane assay was used to determine the effect of NGF on T cell survival. Results Levels of NGF were higher in SF samples from PsA and RA patients as compared to SF samples from OA patients. NGF-induced FLS proliferation was more marked in PsA and RA patients. TrkA was up-regulated on activated SF T cells from PsA (mean ± SD 22 ± 6.2{\%}) and RA (8 ± 1.3{\%}) patients, whereas in SF samples from OA patients, TrkA+CD3+ T cells were not detectable. NGF induced the proliferation of PB T cells, induced the phosphorylation of Akt in activated T cells, and consistent with known pAkt activity, inhibited tumor necrosis factor α-induced cell death in these T cells. Conclusion Based on our findings, we propose a model in which NGF secreted by FLS into PsA and RA synovium promotes the survival of activated autoreactive T cells as well as FLS proliferation. Thus, NGF has the potential to sustain the chronic inflammatory cascades of arthritis of autoimmune origin.",
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