Expression of mRNA TNFα and level of protein TNFα after exposure sCD40L in bone marrow mononuclear cells of myelodysplastic syndromes

Abstract

Background: Cytopenia is the primary phenomenon in myelodysplastic syndrome (MDS) amidst hypercellular bone marrow. The soluble CD40 ligand (sCD40L) is considered as a cytokine that can trigger synthesis of tumor necrosis factor α (TNFα) that promotes apoptosis. The objective of this study is to prove that recombinant human sCD40L (rh-sCD40L) exposure on bone marrow mononuclear cells (BMMC) MDS increases TNFα expression at mRNA level and at protein level.Methods: BMMC from MDS patients whom diagnosed and classified using the WHO 2008 criteria, were exposed to rh-sCD40L and antiCD40L. The expressions of TNFα mRNAs were quantified by qRT-PCR, level of TNFα were measured using the ELISA method.Results: Exposure of rh-sCD40L significantly increased the expression of TNFα mRNA. The similar exposure also significantly increased the level of TNFα compared to controls. TNFα mRNA expression on BMMC in MDS samples exposed to rh-sCD40L is 3.32 times compared to TNFα mRNA expression without exposure. level of TNFα in supernatant media exposed to rh-sCD40L in MDS samples was higher than that of control samples which were 44.44 and 4.85 pg/mL, P=0.018. Conclusions:The sCD40L plays a role in increasing the synthesis of TNFα in mRNA level and protein level in BMMC MDS.

Development of ADS051, an oral, gut‐restricted, small molecule neutrophil modulator for the treatment of neutrophil‐mediated inflammatory diseases

“…We included cytokines (among them IL‐2, IFNγ, and TNFα), whose expression is inhibited by CsA [ 40 ] and which are critical for T‐cell functioning [ 41 ]. Furthermore, we included sCD40L, a cytokine that, upon interaction with CD40, can trigger the synthesis of TNFα and several ILs [ 42 ]. The T‐cell activation assessment revealed a statistically significant lack of T‐cell inhibition by ADS051 at 10 μ m compared with the potent inhibition exhibited by CsA (Fig.…”