LPS priming-induced immune tolerance mitigates LPS-stimulated microglial activation and social avoidance behaviors in mice

被引：5

作者：

Charoensaensuk, Vichuda ^{[1
]}

Huang, Bor-Ren ^{[2
,3
]}

Lin, Chingju ^{[4
]}

Xie, Sheng-Yun ^{[1
]}

Chen, Chao -Wei ^{[5
]}

Chen, Yen -Chang ^{[5
]}

Cheng, Han-Tsung ^{[6
]}

Liu, Yu-Shu ^{[1
]}

Lai, Sheng-Wei ^{[1
]}

Shen, Ching -Kai ^{[7
]}

Lin, Hui -Jung ^{[1
]}

Yang, Liang-Yo ^{[4
,8
,9
]}

Lu, Dah-Yuu ^{[1
,10
]}

机构：

[1] China Med Univ, Sch Med, Dept Pharmacol, Taichung, Taiwan

[2] Taichung Tzu Chi Hosp, Buddhist Tzu Chi Med Fdn, Dept Neurosurg, Taichung, Taiwan

[3] Tzu Chi Univ, Sch Med, Hualien, Taiwan

[4] China Med Univ, Sch Med, Dept Physiol, Taichung 404328, Taiwan

[5] China Med Univ, Inst New Drug Dev, Taichung, Taiwan

[6] China Med Univ Hosp, Dept Surg, Taichung, Taiwan

[7] China Med Univ, Grad Inst Biomed Sci, Taichung, Taiwan

[8] China Med Univ Hosp, Lab Neural Repair, Taichung, Taiwan

[9] China Med Univ Hosp, Biomed Technol R&D Ctr, Taichung 404327, Taiwan

[10] Asia Univ, Dept Photon & Commun Engn, Taichung, Taiwan

来源：

JOURNAL OF PHARMACOLOGICAL SCIENCES | 2024年 / 154卷 / 04期

关键词：

LPS tolerance; Neuroinflammation; Microglial cells; Behavior dysfunction; Proinflammatory cytokines; ENDOTOXIN TOLERANCE; LIPOPOLYSACCHARIDE; NEUROINFLAMMATION; EXPRESSION; ALPHA; NEUROPROTECTION; INFLAMMATION; DEPRESSION; RESPONSES; RECEPTOR;

D O I：

10.1016/j.jphs.2024.02.006

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

In this study, we investigated the regulatory mechanisms underlying the effects of LPS tolerance on the inflammatory homeostasis of immune cells. LPS priming-induced immune tolerance downregulated cyclooxygenase-2, and lowered the production of prostaglandin -E2 in microglial cells. In addition, LPS tolerance downregulated the expression of suppressor of cytokine signaling 3, and inducible nitric oxide synthase/nitric oxide; suppressed the LPS-mediated induction of tumor necrosis factor-alpha, interleukin (IL) -6, and IL -1; and reduced reactive oxygen species production in microglial cells. LPS stimulation increased the levels of the adaptive response-related proteins heme oxygenase-1 and superoxide dismutase 2, and the levels of heme oxygenase-1 (HO -1) enhanced after LPS priming. Systemic administration of low -dose LPS (0.5 mg/kg) to mice for 4 consecutive days attenuated high -dose LPS (5 mg/kg)-induced inflammatory response, microglial activation, and proinflammatory cytokine expression. Moreover, repeated exposure to low -dose LPS suppressed the recruitment of peripheral monocytes or macrophages to brain regions and downregulated the expression of proinflammatory cytokines. Notably, LPS-induced social avoidance behaviors in mice were mitigated by immune tolerance. In conclusion, immune tolerance may reduce proinflammatory cytokine expression and reactive oxygen species production. Our findings provide insights into the effects of endotoxin tolerance on innate immune cells and social behaviors.

引用

页码：225 / 235

页数：11

共 72 条

[1] Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: Clinical implications [J].