Paper Information

Title:  EFFECT OF ANTI-LEPTIN RECEPTOR ANTIBODIES ON LEPTIN SIGNALLING AND LEPTIN-INDUCED TNF-α PRODUCTION
Type: SPEECH
Author(s): JALAEI J.*,ZARKESH E.H.,RAJAEIAN H.,FAZELI M.
 
 *DEPARTMENT OF PHARMACOLOGY, SCHOOL OF VETERINARY MEDICINE, SHIRAZ UNIVERSITY
 
Name of Seminar: IRANIAN CONGRESS OF PHYSIOLOGY AND PHARMACOLOGY
Type of Seminar:  CONGRESS
Sponsor:  PHYSIOLOGY AND PHARMACOLOGY SOCIETY, MASHHAD UNIVERSITY OF MEDICAL SCIENCE
Date:  2007Volume 18
 
 
Abstract: 

Introduction: Leptin as a multifunctional cytokine acts through leptin receptor. Antagonising leptin actions by a specific inhibitor could provide a useful therapy for leptin-associated disorders. Interrupting leptin signalling at the leptin receptor level or signalling cascade events could inhibit leptin functions specifically. In this study, the effect of anti-leptin receptor antibodies, as direct inhibitors, was investigated.
Methods: The anti-human leptin receptor MAbs were screened for leptin antagonist activity using a developed signalling bioassay. MCF-7 cells were pre-treated with antibodies for 30 minutes and treated with various doses of leptin for further 5 hours and the luciferase activity was measured. The impact of 9F8 MAb on TNF-
a production by leptin-stimulated monocytes was assessed by flow cytometry.
Results: Leptin induced about 4-fold increase in SIE activation compared to non-stimulated cells. Pretreatment with 9F8 MAb significantly decreased leptin-induced luciferase activity in a dose dependent manner with the inhibition of 93%±0.8 at 5 µg/ml (p<0.0001), whereas no effect of 4H11, 8C7, and 9G3 MAbs could be observed. None of the anti-leptin receptor MAbs was able to activate leptin signalling pathway. 9F8 MAb inhibited leptin-induced SIE activation even at low doses as 0.5μg/ml (p<0.0001). Application of 9F8 MAb 30 minutes before leptin was found as the best time for 9F8 MAb addition. Leptin caused a great increase in monocyte activation compare to unstimulated cells (p<0.0001). 9F8 MAb was able to inhibit the effect of leptin on monocyte activation as a physiological effect of leptin.
Conclusions: Among the examined antibodies against human leptin receptor, 9F8 was shown to be effective against leptin signalling and leptin-stimulated TNF-
a production by monocytes.

 
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