Expression and significance of AIM2 inflammasome in patients with acute gouty arthritis

doi:10.11958/20231205

Abstract

Abstract:

Objective To investigate the expression and role of melanoma 2 (AIM2), Caspase-1 and gasdermin D (GSDMD) in the pathogenesis of acute gouty arthritis (AGA). Methods Clinical data, biochemical indices and blood samples were collected from 30 patients with AGA (the AGA group) and 30 healthy volunteers (the HC group). Blood cell analyzer was used to detect serum white blood cell count (WBC), hemoglobin (Hb) and platelet count (PLT). Automatic biochemical analyzer was used to detect fasting blood glucose (FBG), blood uric acid (UA), triacylglycerol (TG), total cholesterol (TC), alaine transaminase (ALT), aspartate transaminase (AST), serum creatinine (Scr), blood urea nitrogen (BUN), creatinine clearance rate (Ccr), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels. Fluorescence quantitative assay was used to measure serum level of double-stranded DNA (dsDNA). Western blot was performed to detect the relative protein expression levels of AIM2, Caspase-1, GSDMD, interleukin-1β (IL-1β) and IL-18 in peripheral blood mononuclear cells (PBMCs). Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of IL-1β and IL-18. Results Compared with the HC group, the AGA group showed increased levels of blood biochemical indicators, including WBC, PLT, ESR, CRP, UA, TC, TG, Scr and Ccr (P<0.05). The serum levels of dsDNA, IL-1β and IL-18 were also increased in the AGA group. Furthermore, the relative protein expression levels of AIM2, Caspase-1, GSDMD, IL-1β and IL-18 in PBMCs were all increased (P<0.05). In PBMCs, the protein expression level of AIM2 was positively correlated with that of Caspase-1, GSDMD, IL-1β and IL-18 (r or r_s values were 0.965, 0.986, 0.928 and 0.737, respectively, all P<0.01). Conclusion The expression of AIM2 inflammasome-mediated pyroptosis pathway related molecules (AIM2/Caspase-1/GSDMD) is increased in AGA, which may be involved in the immune inflammatory response of AGA.

Key words: arthritis, gouty, pyroptosis, caspase-1, melanoma deficiency factor 2, pyroporosin D

CLC Number:

R684.3

Figures/Tables 4

References 20

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组别		n	WBC/（×10⁹/L）		Hb/（g/L）		PLT/（×10⁹/L）		ESR/（mm/1 h）	CRP/（mg/L）	UA/（mmol/L）	FBG/（mmol/L）
HC组		30	5.80±1.21		156.23±12.23		226.17±46.58		2.00（2.00，2.00）	0.90（0.58，1.43）	355.10±38.35	5.21（4.83，5.61）
AGA组		30	8.85±1.74		156.90±11.36		276.03±50.67		16.00（8.00，29.00）	14.50（6.85，28.40）	535.37±97.02	5.31（5.00，5.66）
t或Z			7.858^＊＊		0.219		3.968^＊＊		6.165^＊＊	6.353^＊＊	9.465^＊＊	0.806
组别	TC/（mmol/L）			TG/（mmol/L）		ALT/（U/L）		AST/（U/L）		Scr/（μmol/L）	BUN/（mmol/L）	Ccr/（mL/min）
HC组	3.67（3.36，4.48）			0.76（0.65，1.41）		25.50（16.75，29.25）		20.50（18.75，24.25）		82.00（77.75，88.78）	5.17（4.55，5.96）	109.35±18.35
AGA组	5.35（4.65，5.73）			1.83（1.41，2.76）		28.50（21.75，59.25）		22.00（18.00，34.00）		90.50（83.50，98.75）	4.56（3.94，5.22）	125.97±31.27
t或Z	4.739^＊＊			4.709^＊＊		1.746		1.030		2.737^＊＊	2.100^＊	2.511^＊

组别		n	WBC/（×10⁹/L）		Hb/（g/L）		PLT/（×10⁹/L）		ESR/（mm/1 h）	CRP/（mg/L）	UA/（mmol/L）	FBG/（mmol/L）
HC组		30	5.80±1.21		156.23±12.23		226.17±46.58		2.00（2.00，2.00）	0.90（0.58，1.43）	355.10±38.35	5.21（4.83，5.61）
AGA组		30	8.85±1.74		156.90±11.36		276.03±50.67		16.00（8.00，29.00）	14.50（6.85，28.40）	535.37±97.02	5.31（5.00，5.66）
t或Z			7.858^＊＊		0.219		3.968^＊＊		6.165^＊＊	6.353^＊＊	9.465^＊＊	0.806
组别	TC/（mmol/L）			TG/（mmol/L）		ALT/（U/L）		AST/（U/L）		Scr/（μmol/L）	BUN/（mmol/L）	Ccr/（mL/min）
HC组	3.67（3.36，4.48）			0.76（0.65，1.41）		25.50（16.75，29.25）		20.50（18.75，24.25）		82.00（77.75，88.78）	5.17（4.55，5.96）	109.35±18.35
AGA组	5.35（4.65，5.73）			1.83（1.41，2.76）		28.50（21.75，59.25）		22.00（18.00，34.00）		90.50（83.50，98.75）	4.56（3.94，5.22）	125.97±31.27
t或Z	4.739^＊＊			4.709^＊＊		1.746		1.030		2.737^＊＊	2.100^＊	2.511^＊

组别	n	AIM2	Caspase-1	GSDMD	IL-1β	IL-18
HC组	30	0.68±0.05	0.45±0.05	0.60±0.04	0.82±0.04	0.35（0.31，0.36）
AGA组	30	1.45±0.05	0.86±0.05	1.39±0.04	1.01±0.03	1.24（1.21，1.25）
t或Z		59.669^＊＊	31.568^＊＊	79.952^＊＊	19.774^＊＊	6.670^＊＊

组别	n	AIM2	Caspase-1	GSDMD	IL-1β	IL-18
HC组	30	0.68±0.05	0.45±0.05	0.60±0.04	0.82±0.04	0.35（0.31，0.36）
AGA组	30	1.45±0.05	0.86±0.05	1.39±0.04	1.01±0.03	1.24（1.21，1.25）
t或Z		59.669^＊＊	31.568^＊＊	79.952^＊＊	19.774^＊＊	6.670^＊＊

组别	n	IL-1β	IL-18
HC组	30	42.35（31.35，56.35）	82.94±34.01
AGA组	30	57.96（43.15，66.45）	138.54±38.80
t或Z		3.445^＊＊	5.903^＊＊