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Biomed Pharmacother. 2019 Mar;111:359-366. doi: 10.1016/j.biopha.2018.12.093. Epub 2018 Dec 26.

Decreased α7nAChR mRNA levels in peripheral blood monocytes are associated with enhanced inflammatory cytokine production in patients with lupus nephritis.

Author information

1
Obstetric Department, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
2
Urology Center, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
3
Intensive Care Unit, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
4
Department of Rheumatology, The First Hospital of Jilin University, Changchun, Jilin 130021, China.
5
Urology Center, The First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: xu_y@dr.com.

Abstract

The cholinergic anti-inflammatory pathway modulates cytokine release by activating alpha-7 nicotinic acetylcholine receptors (α7nAChR) in monocytes/macrophages. We aimed to determine the role of α7nAChR in lupus nephritis (LN). We enrolled 36 inactive and 35 active LN patients, 34 primary glomerulonephritis patients, and 35 healthy controls. Peripheral blood monocytes were isolated, and mRNA expression of α7nAChR, interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α) in monocytes was measured. α7nAChR and IL-10 mRNA levels were significantly decreased, but IL-6 was increased, in LN patients compared with healthy controls or glomerulonephritis patients (all P < 0.01). Interestingly, α7nAChR mRNA levels were negatively correlated to SLEDAI (r = -0.68, P < 0.01), anti-dsDNA (r = -0.38, P < 0.05), and proteinuria (r = -0.49, P < 0.01) levels, and positively correlated to serum complement C3 levels (r = 0.38, P < 0.05) in patients with active LN. Furthermore, α7nAChR mRNA levels were negatively correlated to TNF-α (r = -0.50, P < 0.01), IL-1β (r = -0.42, P < 0.05), IL-6 (r = -0.69, P < 0.01) mRNA levels, and positively correlated to IL-10 (r = 0.45, P < 0.01). TNF-α, IL-1β, and IL-6 protein levels in the supernatant of cultured monocytes from active LN patients were significantly higher, while IL-10 was lower, than that of healthy controls. PNU-282987, an α7nAChR agonist, significantly decreased TNF-α, IL-1β, and IL-6 but increased IL-10 in the monocyte culture supernatant of active LN patients, which were abolished by an α7nAChR antagonist methyllycaconitine. The effects of PNU-282987 were confirmed in lipopolysaccharides-stimulated monocytes. Taken together, these findings suggest that decrease in α7nAChR mRNA levels may play a role in LN and that activation of α7nAChR may inhibit inflammation in LN.

KEYWORDS:

Cytokine; Inflammation; Lupus nephritis; Peripheral monocyte; α7nAChR

PMID:
30594048
DOI:
10.1016/j.biopha.2018.12.093
[Indexed for MEDLINE]
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