Abstract
Background: Hypoxia-induced activation of nuclear factor kappa B (NFkappaB) modulates the transcription of multiple target genes. A transmembrane receptor of the tumor necrosis factor (TNF) gene superfamily CD40 orchestrates the process of inflammation through secondary messengers - mitogen activated protein kinase kinase 4 (MKK4) and c-Jun NH2-terminal kinases (JNK).
Objectives: We analyzed the effects of obstructive sleep apnoea (OSA) on serum TNFalpha and its soluble receptors (sTNF-RI, sTNF-RII), and on adipose tissue (AT) NFkappaB, CD40, MKK4 and JNK mRNA expressions.
Methods: 25 male subjects (17 with severe OSA, 8 controls) underwent overnight polysomnography. Samples of subcutaneous AT were analyzed using rtPCR.
Results: Circulatory sTNF-RI and sTNF-RII correlated directly with transcutaneous O2 saturation <90% (R=0.458, p=0.003; R=0.335, p=0.035); sTNF-RII correlated also with apnoea-hypopnoea and oxygen desaturation indices (R=0.358, p=0.024; R=0.324, p=0.041). Compared to controls, patients with OSA had significantly lower AT expressions of CD40, MKK4 and JNK [1.03±0.3 vs 1.34±0.3 ΔΔCt, p=0.026; 1.06±0.28 vs 1.38±0.17 ΔΔCt, p=0.005; 1.09±0.45 vs 1.48±0.37 ΔΔCt, p=0.037, respectively]. No differences were observed in NFkappaBI, NFkappaBII or TNFalpha AT expressions between the two groups.
Conclusions: In OSA, systemic inflammation reflected by increases in serum sTNF-RII is not related to AT CD40, MKK4 and JNK gene expressions. Further studies are needed to explore the role of intermittent hypoxia in systemic inflammation in patients with OSA.
Funding: APVV-0134-11, VEGA 1/0111/12, Slovakia.
- © 2014 ERS