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The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview

Abstract

Rheumatoid arthritis (RA) is a chronic, autoimmune, inflammatory disease destroying articular cartilage and bone. The female preponderance and the influence of reproductive states in RA have long linked this disease to sexually dimorphic, reproductive hormones such as prolactin (PRL). PRL has immune-enhancing properties and increases in the circulation of some patients with RA. However, PRL also suppresses the immune system, stimulates the formation and survival of joint tissues, acquires antiangiogenic properties upon its cleavage to vasoinhibins, and protects against joint destruction and inflammation in the adjuvant-induced model of RA. This review addresses risk factors for RA linked to PRL, the effects of PRL and vasoinhibins on joint tissues, blood vessels, and immune cells, and the clinical and experimental data associating PRL with RA. This information provides important insights into the pathophysiology of RA and highlights protective actions of the PRL/vasoinhibin axis that could lead to therapeutic benefits.

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Abbreviations

RA:

Rheumatoid arthritis

PRL:

Prolactin

ACPA:

Anti-citrullinated peptide antibodies

RF:

Rheumatoid factor

TRAF1-C5:

Tumor necrosis factor receptor-associated factor 1

STAT:

Signal transducer and activator of transcription

NF-κβ:

Nuclear factor κβ

Th1:

T helper 1

Th2:

T helper 2

IL:

Interleukin

IFNγ:

Interferon γ

TNF α:

Tumor necrosis factor α

JAK:

Janus kinase

PI3k:

Phosphatidylinositol 3-kinase

MAPK:

Mitogen-activated protein kinase

BMP-1:

Bone morphogenetic protein-1

RANKL:

Receptor activator of NF-κβ ligand

VEGF:

Vascular endothelial growth factor

FGF-2:

Fibroblast growth factor-2

HO-1:

Heme oxigenase-1

BK:

Bradykinin

ACh:

Acetylcholine

PAI-1:

Plasminogen activator inhibitor-1

uPA:

Urokinase plasminogen activator

uPAR :

Urokinase plasminogen activator receptor

eNOS:

Endothelial nitric oxide synthase

PP2A:

Protein phosphatase 2A

TRPC5:

Transient receptor potential channel 5

PRLR:

Prolactin receptor

NK:

Natural killer

iNOS:

Inducible nitric oxide synthase

NO:

Nitric oxide

TRH:

Thyrotropin-releasing hormone

TIMP-1:

Tissue inhibitor of MMP

CFA:

Complete Freund´s adjuvant

AP:

Anterior pituitary gland

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Acknowledgments

We thank Fernando Lopez-Barrera, Gabriel Nava, and Francisco Javier Valles Valenzuela for their technical assistance, Guadalupe Calderon for artistic contribution, and Dorothy D. Pless for critically editing the manuscript. N. Adan, M.G. Ledesma-Colunga, and M. Solis-Gutierrez were supported by fellowships from the Council of Science and Technology of Mexico (CONACYT) and the Ph.D. Program in Biomedical Sciences of the National University of Mexico (UNAM). The study was supported by UNAM Grant IN201315 to C. Clapp.

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Clapp, C., Adán, N., Ledesma-Colunga, M.G. et al. The role of the prolactin/vasoinhibin axis in rheumatoid arthritis: an integrative overview. Cell. Mol. Life Sci. 73, 2929–2948 (2016). https://doi.org/10.1007/s00018-016-2187-0

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Keywords

  • Gender
  • Stress
  • Reproduction
  • Angiogenesis
  • Joint tissues
  • Immune cells
  • Cartilage
  • Bone
  • Blood vessels