Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis

Vikram Haridas, Praveenkumar Shetty, E. Sarathkumar, Anil Bargale, Jamboor K. Vishwanatha, Vidya Patil, U. S. Dinesh

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Annexin A2 has been implicated in several immune modulated diseases including Rheumatoid arthritis (RA) pannus formation. The most relied treatment option for RA pathogenesis is glucocorticoids. Glucocorticoids regulate the synthesis, phosphorylation and cellular deposition of Annexin A1. This annexin mediates the anti-inflammatory actions of glucocorticoids. These two first characterized members of annexin superfamily proteins acts reciprocally, one as an anti-inflammatory and the other proinflammatory in nature. The possibility of these molecules as soluble biomarkers and as an upstream regulator of major cytokine devastation at RA microenvironment has not been previously explored. Current study elucidates the reciprocal regulation of these two annexins in RA pathogenesis. These Annexin A2/A1 and downstream cytokines in RA serum were analysed by ELISA. Western blot, Immunocytochemistry, immunoprecipitation and Immunohistochemistry were adapted to analyse these molecules in tissue and synovial fibroblasts and also in different experimental conditions. Significant increase in the level of Annexin A2 was noticed in naïve RA patients compared to controls (14.582 ± 1.766 ng/ml vs. 7.37 ± 1.450 ng/ml; p ≤ 0.001). In remission cases significant low levels was detected. On the contrary, significant decrease in the level of Annexin A1 was noticed in naïve RA patients compared to healthy controls (12.322 ± 2.91 vs. 16.998 ± 4.298 ng/ml; p ≤ 0.001), wherein remission cases serum Annexin A1 was significantly high. The knockdown of proinflammatory Annexin A2 by siRNA/antibody treatment could mimic the glucocorticoid treatment as which induced cellular Annexin A1 and membrane translocation resulting in the terminal action. Current data elucidating the regulatory interplay between Annexin A2 and Annexin A1 in RA pathogenesis.

Original languageEnglish
Pages (from-to)83-95
Number of pages13
JournalMolecular Biology Reports
Volume46
Issue number1
DOIs
StatePublished - 1 Feb 2019

Fingerprint

Annexin A2
Annexin A1
Rheumatoid Arthritis
Anti-Inflammatory Agents
Annexins
Glucocorticoids
Immunohistochemistry
Cytokines
Immune System Diseases
Serum
Immunoprecipitation
Small Interfering RNA
Therapeutics
Fibroblasts
Biomarkers
Western Blotting
Enzyme-Linked Immunosorbent Assay
Phosphorylation
Membranes

Keywords

  • Annexin A1
  • Annexin A2
  • Inflammatory cytokines
  • Proinflammatory mediators
  • Rheumatoid arthritis

Cite this

Haridas, Vikram ; Shetty, Praveenkumar ; Sarathkumar, E. ; Bargale, Anil ; Vishwanatha, Jamboor K. ; Patil, Vidya ; Dinesh, U. S. / Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis. In: Molecular Biology Reports. 2019 ; Vol. 46, No. 1. pp. 83-95.
@article{257d6e6e77b44137a13360efe695eb11,
title = "Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis",
abstract = "Annexin A2 has been implicated in several immune modulated diseases including Rheumatoid arthritis (RA) pannus formation. The most relied treatment option for RA pathogenesis is glucocorticoids. Glucocorticoids regulate the synthesis, phosphorylation and cellular deposition of Annexin A1. This annexin mediates the anti-inflammatory actions of glucocorticoids. These two first characterized members of annexin superfamily proteins acts reciprocally, one as an anti-inflammatory and the other proinflammatory in nature. The possibility of these molecules as soluble biomarkers and as an upstream regulator of major cytokine devastation at RA microenvironment has not been previously explored. Current study elucidates the reciprocal regulation of these two annexins in RA pathogenesis. These Annexin A2/A1 and downstream cytokines in RA serum were analysed by ELISA. Western blot, Immunocytochemistry, immunoprecipitation and Immunohistochemistry were adapted to analyse these molecules in tissue and synovial fibroblasts and also in different experimental conditions. Significant increase in the level of Annexin A2 was noticed in na{\"i}ve RA patients compared to controls (14.582 ± 1.766 ng/ml vs. 7.37 ± 1.450 ng/ml; p ≤ 0.001). In remission cases significant low levels was detected. On the contrary, significant decrease in the level of Annexin A1 was noticed in na{\"i}ve RA patients compared to healthy controls (12.322 ± 2.91 vs. 16.998 ± 4.298 ng/ml; p ≤ 0.001), wherein remission cases serum Annexin A1 was significantly high. The knockdown of proinflammatory Annexin A2 by siRNA/antibody treatment could mimic the glucocorticoid treatment as which induced cellular Annexin A1 and membrane translocation resulting in the terminal action. Current data elucidating the regulatory interplay between Annexin A2 and Annexin A1 in RA pathogenesis.",
keywords = "Annexin A1, Annexin A2, Inflammatory cytokines, Proinflammatory mediators, Rheumatoid arthritis",
author = "Vikram Haridas and Praveenkumar Shetty and E. Sarathkumar and Anil Bargale and Vishwanatha, {Jamboor K.} and Vidya Patil and Dinesh, {U. S.}",
year = "2019",
month = "2",
day = "1",
doi = "10.1007/s11033-018-4448-5",
language = "English",
volume = "46",
pages = "83--95",
journal = "Molecular Biology Reports",
issn = "0301-4851",
publisher = "Springer Netherlands",
number = "1",

}

Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis. / Haridas, Vikram; Shetty, Praveenkumar; Sarathkumar, E.; Bargale, Anil; Vishwanatha, Jamboor K.; Patil, Vidya; Dinesh, U. S.

In: Molecular Biology Reports, Vol. 46, No. 1, 01.02.2019, p. 83-95.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Reciprocal regulation of pro-inflammatory Annexin A2 and anti-inflammatory Annexin A1 in the pathogenesis of rheumatoid arthritis

AU - Haridas, Vikram

AU - Shetty, Praveenkumar

AU - Sarathkumar, E.

AU - Bargale, Anil

AU - Vishwanatha, Jamboor K.

AU - Patil, Vidya

AU - Dinesh, U. S.

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Annexin A2 has been implicated in several immune modulated diseases including Rheumatoid arthritis (RA) pannus formation. The most relied treatment option for RA pathogenesis is glucocorticoids. Glucocorticoids regulate the synthesis, phosphorylation and cellular deposition of Annexin A1. This annexin mediates the anti-inflammatory actions of glucocorticoids. These two first characterized members of annexin superfamily proteins acts reciprocally, one as an anti-inflammatory and the other proinflammatory in nature. The possibility of these molecules as soluble biomarkers and as an upstream regulator of major cytokine devastation at RA microenvironment has not been previously explored. Current study elucidates the reciprocal regulation of these two annexins in RA pathogenesis. These Annexin A2/A1 and downstream cytokines in RA serum were analysed by ELISA. Western blot, Immunocytochemistry, immunoprecipitation and Immunohistochemistry were adapted to analyse these molecules in tissue and synovial fibroblasts and also in different experimental conditions. Significant increase in the level of Annexin A2 was noticed in naïve RA patients compared to controls (14.582 ± 1.766 ng/ml vs. 7.37 ± 1.450 ng/ml; p ≤ 0.001). In remission cases significant low levels was detected. On the contrary, significant decrease in the level of Annexin A1 was noticed in naïve RA patients compared to healthy controls (12.322 ± 2.91 vs. 16.998 ± 4.298 ng/ml; p ≤ 0.001), wherein remission cases serum Annexin A1 was significantly high. The knockdown of proinflammatory Annexin A2 by siRNA/antibody treatment could mimic the glucocorticoid treatment as which induced cellular Annexin A1 and membrane translocation resulting in the terminal action. Current data elucidating the regulatory interplay between Annexin A2 and Annexin A1 in RA pathogenesis.

AB - Annexin A2 has been implicated in several immune modulated diseases including Rheumatoid arthritis (RA) pannus formation. The most relied treatment option for RA pathogenesis is glucocorticoids. Glucocorticoids regulate the synthesis, phosphorylation and cellular deposition of Annexin A1. This annexin mediates the anti-inflammatory actions of glucocorticoids. These two first characterized members of annexin superfamily proteins acts reciprocally, one as an anti-inflammatory and the other proinflammatory in nature. The possibility of these molecules as soluble biomarkers and as an upstream regulator of major cytokine devastation at RA microenvironment has not been previously explored. Current study elucidates the reciprocal regulation of these two annexins in RA pathogenesis. These Annexin A2/A1 and downstream cytokines in RA serum were analysed by ELISA. Western blot, Immunocytochemistry, immunoprecipitation and Immunohistochemistry were adapted to analyse these molecules in tissue and synovial fibroblasts and also in different experimental conditions. Significant increase in the level of Annexin A2 was noticed in naïve RA patients compared to controls (14.582 ± 1.766 ng/ml vs. 7.37 ± 1.450 ng/ml; p ≤ 0.001). In remission cases significant low levels was detected. On the contrary, significant decrease in the level of Annexin A1 was noticed in naïve RA patients compared to healthy controls (12.322 ± 2.91 vs. 16.998 ± 4.298 ng/ml; p ≤ 0.001), wherein remission cases serum Annexin A1 was significantly high. The knockdown of proinflammatory Annexin A2 by siRNA/antibody treatment could mimic the glucocorticoid treatment as which induced cellular Annexin A1 and membrane translocation resulting in the terminal action. Current data elucidating the regulatory interplay between Annexin A2 and Annexin A1 in RA pathogenesis.

KW - Annexin A1

KW - Annexin A2

KW - Inflammatory cytokines

KW - Proinflammatory mediators

KW - Rheumatoid arthritis

UR - http://www.scopus.com/inward/record.url?scp=85056456763&partnerID=8YFLogxK

U2 - 10.1007/s11033-018-4448-5

DO - 10.1007/s11033-018-4448-5

M3 - Article

VL - 46

SP - 83

EP - 95

JO - Molecular Biology Reports

JF - Molecular Biology Reports

SN - 0301-4851

IS - 1

ER -