Title:Estriol Inhibits Dermcidin Isoform-2 Induced Inflammatory Cytokine Expression Via Nitric Oxide Synthesis in Human Neutrophil
Volume: 18
Issue: 10
Author(s): Pradipta Jana, Md. Mobidullah Khan, Subrata Kumar De, Asru K. Sinha, Santanu Guha, Gausal A. Khan and Smarajit Maiti*
Affiliation:
- Post Graduate Department of Biochemistry, Cell & Molecular Therapeutics Laboratory, Oriental Institute of Science and Technology, Rangamati, Midnapore, WB, 721102,India
Keywords:
Acute ischemic heart disease, Inflammation, TNF-α, IL-6, Dermcidin isoform-2, leukocytes.
Abstract: Background: An increase in the level of cytokines like TNF-α and IL-6
causes the inflammatory surge in acute ischemic heart disease (AIHD).
Objective: A high-level dermcidin isoform-2 (DCN-2) occurrence in AIHD was subjected
to determine a possible regulation of cytokines expression. The effect of estrogen to
counteract the inflammatory response was determined.
Methods: Blood was collected from AIHD patients and normal volunteers with consent.
Nitric oxide (NO) synthesis was done with methemoglobin method.TNF-α and IL-6
expression were determined by ELISA and Western blot.
Results: (DCN-2) incubation with 120nM to the normal neutrophil solution for 2h
resulted in the increase of TNF-α from 3.82±1.53pg/ml to 20.7±6.9pg/ml and IL-6 from
3.27±1.52pg/ml to 47.07±3.4pg/ml. In AIHD patients, the cytokine level was18.3-
27.3pg/ml, with a median value 21.86pg/ml (TNF-α) and IL-6 level was 23.54-
52.73pg/ml, with a median value 42.16pg/ml. Treatment with 0.6nM estriol, a kind of
female steroid hormone estrogen for 45min decreased the elevated cytokine level in
120nM DCN-2 treated normal neutrophils. DCN-2 induced TNF-α synthesis in
neutrophils was further determined by Western blot technique with a thickened band
intensity of TNF-α. Estriol (0.6nM) treatment also influenced the DCN-2 induced
inhibition of nitric oxide (NO) synthesis from 0nmol NO/ml to 0.56nmol/ml. The
subsequent reduction of TNF-α level correlates the increase of NO level.
Conclusion: In conclusion, the stress-induced DCN-2 production in AIHD propagates
the inflammatory response. Steroid molecule like estriol plays a protective role by
reducing DCN-2 responses in the NO synthesis.