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Molecular and Cellular Biochemistry

, Volume 394, Issue 1–2, pp 67–75 | Cite as

N-(2-hydroxy phenyl) acetamide: a novel suppressor of Toll-like receptors (TLR-2 and TLR-4) in adjuvant-induced arthritic rats

  • Kahkashan Perveen
  • Farina Hanif
  • Huma Jawed
  • Siddiqua Jamall
  • Shabana Usman Simjee
Article

Abstract

Toll-like receptors (TLRs) are key recognition structures of immune system and recently emerged as potential contributors to the inflammation observed in human and rodent models of arthritis. Present study aims to investigate the effect of N-(2-hydroxy phenyl)-acetamide (NA-2) on modulation of TLRs in the development of adjuvant-induced arthritis. Arthritis was induced by intradermal administration of heat-killed Mycobacterium tuberculosis H37Ra. The treatment of NA-2 (5 mg/kg) and indomethacin (5 mg/kg) was started in their respective group on the day of arthritis induction. Body weights, paw volume measurements, and nociception sensation (Plantar test) were done on alternate days to monitor the progression of the disease until arthritis score of four was observed in arthritic control group. Along with the clinical signs, histopathology of knee joints was also performed. The splenocytes cultures were prepared from each group; TLR-2 and TLR-4 mRNAs were analyzed in 48-h cultured splenocytes using RT-PCR; and the supernatants were used to determine IL-1β and TNF-α by ELISA. A significant reversal of deficit seen in body weights of the arthritic control group was observed in NA-2-treated animals with a parallel decrease in paw edema and transmission of nociception. Remission of the clinical signs and nociception was associated with improved histology. Compared with arthritic control, NA-2 treatment significantly decreased the level of IL-1β (p < 0.003) and TNF-α (p < 0.001) in the supernatants of cultured splenocytes. Likewise, NA-2 also reduced the expression of TLRs mRNA. Our findings suggest that NA-2 affects AIA in a pleiotropic manner, suppressing TLRs-mediated joint inflammation and related symptoms.

Keywords

Toll-like receptor Tumor necrosis factor Interleukin-1 Inflammation N-(2-hydroxy phenyl) acetamide Rheumatoid arthritis 

Notes

Conflicts of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Kahkashan Perveen
    • 1
  • Farina Hanif
    • 1
  • Huma Jawed
    • 2
  • Siddiqua Jamall
    • 3
  • Shabana Usman Simjee
    • 1
    • 2
  1. 1.Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan
  2. 2.H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological SciencesUniversity of KarachiKarachiPakistan
  3. 3.Department of BiochemistryUniversity of KarachiKarachiPakistan

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