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Low shear stress induced HMGB1 translocation and release via PECAM-1/PARP-1 pathway to induce inflammation response.

Qin WD, Mi SH, Li C, Wang GX, Zhang JN, Wang H, Zhang F, Ma Y, Wu DW, Zhang M - PLoS ONE (2015)

Bottom Line: Inhibition of HGMB1 reduced LSS-induced inflammatory response.LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway.PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression.

View Article: PubMed Central - PubMed

Affiliation: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.

ABSTRACT
Low shear stress (LSS) plays a critical role in the site predilection of atherosclerosis through activation of cellular mechanosensors, such as platelet endothelial cell adhesion molecule 1 (PECAM-1). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that regulates the expression of various inflammatory cytokines. The nuclear enzyme high mobility group box 1 (HMGB1) can induce inflammation response by binding to toll-like receptor 4 (TLR4). In the present study, we aimed to investigate the role and mechanism of HMGB1 in LSS induced inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated by undisturbed shear stress (USS, 1 Pa) and LSS (0.4 Pa) in our experiments. Gene expression was inhibited by small interfering RNA (siRNA). ICAM-1 expression was regulated by LSS in a time dependent manner. LSS can induce HMGB1 translocation from nucleus to cytoplasm and release. Compared with the USS, LSS could increase the protein expression of PECAM-1 and PARP-1 as well as the secretion of TNF-α and IL-1β. LSS induced the translocation of HMGB1 from nucleus to cytoplasm. Inhibition of HGMB1 reduced LSS-induced inflammatory response. Inhibition of PARP-1 suppressed inflammatory response through inhibiting TLR4 expression and HMGB1 translocation. PECAM-1 inhibition reduced LSS-induced ICAM-1 expression, TNF-α and IL-1β secretion, and monocytes adhesion. LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway. PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression. Inhibition of PARP-1 may shed light on the treatment of HMGB1 involved inflammation during atherosclerosis.

No MeSH data available.


Related in: MedlinePlus

HMGB1 inhibition reduced LSS-induced inflammatory response.HMGB1 inhibition reduced LSS-induced inflammatory response, including ICAM-1 mRNA and protein expression, TNF-α and IL-1β secretion and monocytes adhesion. (A, B, C) The mRNA and protein expression of ICAM-1 were assessed by RT-PCR and western blot analysis. (D) TNF-α secretion was assessed by ELISA. (E) IL-1β secretion was assessed by ELISA. (F) THP-1 monocytes adhesion. Values are expressed as mean ± S.D. from three separate experiments. *P<0.05 vs. USS. #P<0.05 vs. LSS; si-HMGB1: HMGB1 siRNA; si-NC: negative control of HMGB1 siRNA.
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pone.0120586.g003: HMGB1 inhibition reduced LSS-induced inflammatory response.HMGB1 inhibition reduced LSS-induced inflammatory response, including ICAM-1 mRNA and protein expression, TNF-α and IL-1β secretion and monocytes adhesion. (A, B, C) The mRNA and protein expression of ICAM-1 were assessed by RT-PCR and western blot analysis. (D) TNF-α secretion was assessed by ELISA. (E) IL-1β secretion was assessed by ELISA. (F) THP-1 monocytes adhesion. Values are expressed as mean ± S.D. from three separate experiments. *P<0.05 vs. USS. #P<0.05 vs. LSS; si-HMGB1: HMGB1 siRNA; si-NC: negative control of HMGB1 siRNA.

Mentions: To confirm our hypothesis that LSS induced inflammatory response via HMGB1, we used HMGB1 siRNA in the following experiments. Firstly we verified the validity of HMGB1 siRNA. The RT-PCR and western blot analysis showed that the mRNA and protein expression of HMGB1 was significantly reduced by siRNA (S1 Fig.). After HMGB1 was inhibited by siRNA, HUVECs were exposed to LSS. Compared with USS, LSS increased ICAM-1 expression, while HMGB1 inhibition decreased LSS-induced ICAM-1 expression (Fig. 3A-3C). Meanwhile, LSS could significantly increase the TNF-α and IL-1β secretion as well as the number of adhesional THP-1 cells, while HMGB1 inhibition reduced the inflammatory response (Fig. 3D-3F). The results suggested that HMGB1 played a critical role in LSS induced inflammation response.


Low shear stress induced HMGB1 translocation and release via PECAM-1/PARP-1 pathway to induce inflammation response.

Qin WD, Mi SH, Li C, Wang GX, Zhang JN, Wang H, Zhang F, Ma Y, Wu DW, Zhang M - PLoS ONE (2015)

HMGB1 inhibition reduced LSS-induced inflammatory response.HMGB1 inhibition reduced LSS-induced inflammatory response, including ICAM-1 mRNA and protein expression, TNF-α and IL-1β secretion and monocytes adhesion. (A, B, C) The mRNA and protein expression of ICAM-1 were assessed by RT-PCR and western blot analysis. (D) TNF-α secretion was assessed by ELISA. (E) IL-1β secretion was assessed by ELISA. (F) THP-1 monocytes adhesion. Values are expressed as mean ± S.D. from three separate experiments. *P<0.05 vs. USS. #P<0.05 vs. LSS; si-HMGB1: HMGB1 siRNA; si-NC: negative control of HMGB1 siRNA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4368774&req=5

pone.0120586.g003: HMGB1 inhibition reduced LSS-induced inflammatory response.HMGB1 inhibition reduced LSS-induced inflammatory response, including ICAM-1 mRNA and protein expression, TNF-α and IL-1β secretion and monocytes adhesion. (A, B, C) The mRNA and protein expression of ICAM-1 were assessed by RT-PCR and western blot analysis. (D) TNF-α secretion was assessed by ELISA. (E) IL-1β secretion was assessed by ELISA. (F) THP-1 monocytes adhesion. Values are expressed as mean ± S.D. from three separate experiments. *P<0.05 vs. USS. #P<0.05 vs. LSS; si-HMGB1: HMGB1 siRNA; si-NC: negative control of HMGB1 siRNA.
Mentions: To confirm our hypothesis that LSS induced inflammatory response via HMGB1, we used HMGB1 siRNA in the following experiments. Firstly we verified the validity of HMGB1 siRNA. The RT-PCR and western blot analysis showed that the mRNA and protein expression of HMGB1 was significantly reduced by siRNA (S1 Fig.). After HMGB1 was inhibited by siRNA, HUVECs were exposed to LSS. Compared with USS, LSS increased ICAM-1 expression, while HMGB1 inhibition decreased LSS-induced ICAM-1 expression (Fig. 3A-3C). Meanwhile, LSS could significantly increase the TNF-α and IL-1β secretion as well as the number of adhesional THP-1 cells, while HMGB1 inhibition reduced the inflammatory response (Fig. 3D-3F). The results suggested that HMGB1 played a critical role in LSS induced inflammation response.

Bottom Line: Inhibition of HGMB1 reduced LSS-induced inflammatory response.LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway.PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression.

View Article: PubMed Central - PubMed

Affiliation: The Department of Critical Care Unit, Qilu Hospital of Shandong University, Jinan, Shandong, China.

ABSTRACT
Low shear stress (LSS) plays a critical role in the site predilection of atherosclerosis through activation of cellular mechanosensors, such as platelet endothelial cell adhesion molecule 1 (PECAM-1). Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme that regulates the expression of various inflammatory cytokines. The nuclear enzyme high mobility group box 1 (HMGB1) can induce inflammation response by binding to toll-like receptor 4 (TLR4). In the present study, we aimed to investigate the role and mechanism of HMGB1 in LSS induced inflammation in human umbilical vein endothelial cells (HUVECs). HUVECs were stimulated by undisturbed shear stress (USS, 1 Pa) and LSS (0.4 Pa) in our experiments. Gene expression was inhibited by small interfering RNA (siRNA). ICAM-1 expression was regulated by LSS in a time dependent manner. LSS can induce HMGB1 translocation from nucleus to cytoplasm and release. Compared with the USS, LSS could increase the protein expression of PECAM-1 and PARP-1 as well as the secretion of TNF-α and IL-1β. LSS induced the translocation of HMGB1 from nucleus to cytoplasm. Inhibition of HGMB1 reduced LSS-induced inflammatory response. Inhibition of PARP-1 suppressed inflammatory response through inhibiting TLR4 expression and HMGB1 translocation. PECAM-1 inhibition reduced LSS-induced ICAM-1 expression, TNF-α and IL-1β secretion, and monocytes adhesion. LSS can induce inflammatory response via PECAM-1/PARP-1/HMGB1 pathway. PARP-1 plays a fundamental role in HMGB1 translocation and TLR4 expression. Inhibition of PARP-1 may shed light on the treatment of HMGB1 involved inflammation during atherosclerosis.

No MeSH data available.


Related in: MedlinePlus