Transcriptional regulation of VCAM‐1 expression by tumor necrosis factor‐α in human tracheal smooth muscle cells: Involvement of MAPKs, NF‐κB, p300, and histone acetylation

Luo

The American Journal of Pathology

et al. 2009

Self Cite

157

151

Oxidative stresses are believed to play an important role in the induction of both cell adhesion molecules and pro-inflammatory cytokines, a key event in a variety of inflammatory processes. The enzyme heme oxygenase-1 (HO-1) functions as an antioxidant and serves to protect against tissue injury. In this study, we report that HO-1 was induced in cultured human tracheal smooth muscle cells after either treatment with a potent inducer of HO-1 activity, cobalt protoporphyrin IX, or infection with a recombinant adenovirus that carries the human HO-1 gene. Overexpression of HO-1 protected against tumor necrosis factor (TNF)-␣-mediated airway inflammation via the down-regulation of oxidative stress, adhesion molecules, and interleukin-6 in both cultured human tracheal smooth muscle cells and the airways of mice. In addition, HO-1 overexpression inhibited TNF-␣-induced intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 expression, adherence of THP-1 cells, generation of interleukin-6, p47 phox translocation, and nuclear factor-B activation. HO-1 overexpression also attenuated TNF-␣-induced oxidative stress, which was abrogated in the presence of both the HO-1 inhibitor, zinc protoporphyrin IX, as well as a carbon monoxide scavenger. In addition, HO-1 overexpression reduced the formation of a TNFR1/c-Src/p47 phox complex. These results suggest that HO-1 functions as a suppressor of TNF-␣ signaling, not only by inhibiting the expression of adhesion molecules and generation of interleukin-6, but also by diminishing intracellular reactive oxygen species production and nuclear factor-B activation in both cultured human tracheal smooth muscle cells and the airways of mice.

Section: Reverse Transcription-pcr Analysismentioning

confidence: 99%

“…ICAM-1-luc or VCAM-1-luc activity was determined as previously described using a luciferase assay system (Promega, Madison, WI). 17 …”

Section: Measurement Of Icam-1 and Vcam-1 Luciferase Activitymentioning

confidence: 99%

Overexpression of HO-1 Protects against TNF-α-Mediated Airway Inflammation by Down-Regulation of TNFR1-Dependent Oxidative Stress

Luo

The American Journal of Pathology

et al. 2009

Self Cite

157

151

“…Similarly, VCAM‐1 contributes to macrophage accumulation in developing lesions 61. The reduction in MCP‐1 and VCAM‐1 expression is most likely the consequence of reduced T cell and macrophage activation; macrophage and T cell‐derived cytokines are reduced by RMT1‐10 treatment and tumor necrosis factorα, IL‐6 and IL‐1β are potent inducers of MCP‐1 expression,62, 63, 64 whilst tumor necrosis factor‐α and IL‐1β are also known to induce VCAM‐1 expression 65, 66…”

Section: Discussionmentioning

confidence: 99%

Anti‐TIM‐1 Monoclonal Antibody (RMT1‐10) Attenuates Atherosclerosis By Expanding IgM‐producing B1a Cells

Hosseini

Kanellakis

et al. 2018

JAHA

BackgroundPeritoneal B1a cells attenuate atherosclerosis by secreting natural polyclonal immunoglobulin M (IgM). Regulatory B cells expressing T‐cell immunoglobulin mucin domain‐1 (TIM‐1) expanded through TIM‐1 ligation by anti‐TIM‐1 monoclonal antibody (RMT1‐10) induces immune tolerance.Methods and ResultsWe examined the capacity of RMT1‐10 to expand peritoneal B1a cells to prevent atherosclerosis development and retard progression of established atherosclerosis. RMT1‐10 treatment selectively doubled peritoneal B1a cells, tripled TIM‐1+ B1a cells and increased TIM‐1+IgM+interleukin (IL)‐10+ by 3‐fold and TIM‐1+IgM+IL‐10− B1a cells by 2.5‐fold. Similar expansion of B1a B cells was observed in spleens. These effects reduced atherosclerotic lesion size, increased plasma IgM and lesion IgM deposits, and decreased oxidatively modified low‐density lipoproteins in lesions. Lesion CD4+ and CD8+ T cells, macrophages and monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, expression of proinflammatory cytokines monocyte chemoattractant protein‐1, vascular cell adhesion molecule‐1, IL1β, apoptotic cell numbers and necrotic cores were also reduced. RMT1‐10 treatment failed to expand peritoneal B1a cells and reduce atherosclerosis after splenectomy that reduces B1a cells, indicating that these effects are B1a cell‐dependent. Apolipoprotein E‐KO mice fed a high‐fat diet for 6 weeks before treatment with RMT1‐10 also increased TIM‐1+IgM+ IL‐10+ and TIM‐1+IgM+ IL‐10− B1a cells and IgM levels and attenuated progression of established atherosclerosis.Conclusions RMT1‐10 treatment attenuates atherosclerosis development and progression by selectively expanding IgM producing atheroprotective B1a cells. Antibody‐based in vivo expansion of B1a cells could be an attractive approach for treating atherosclerosis.

“…It has been well established that inflammatory responses following exposure to cytokines are highly dependent on activation of NF-κB, which plays an important role in expression of several inflammatory genes (4,24,25). Previous studies also demonstrated that activation of NF-κB is essential for expression of VCAM-1 induced by TNF-α in human tracheal smooth muscle cells (20). Besides, VCAM-1 promoters contain NF-κB binding sites, which are regulated through MAPKs in several cell types (26).…”

Section: Discussionmentioning

confidence: 99%

“…VCAM-1 was not expressed on resting vascular endothelium, but was rapidly induced in response to a number of inflammatory stimuli, consistent with our observation that VCAM-1 expression was maintained at a low level and 700, 1,000, 1,400 µM MSU induced a dose-and time-dependent increase of VCAM-1 expression. Expression of VCAM-1 has been reported to be highly regulated by MAPKs and NF-κB (20)(21)(22). To find out signaling pathways that mediate increased VCAM-1 expression in human synovial cells, we performed Western blotting to examine the activation of several signaling molecules including 3 MAPKs (ERK1/2, p38 MAPK, and JNK), and PPARγ.…”

Section: Discussionmentioning

confidence: 99%

Involvement of mitogen-activated protein kinases and peroxisome proliferator-activated receptor γ in monosodium urate crystal-induced vascular cell adhesion molecule 1 expression in human rheumatoid arthritis synovial fibroblasts

2012

Abstract. To investigate whether monosodium urate (MSU) crystals could induce the production of VCAM-1 (vascular cell adhesion molecule 1) in human synovial cells and its possible signaling pathways, human synovial cells isolated from synovial tissue explants were stimulated with various doses of MSU crystals for different time intervals. Expression of VCAM-1 was evaluated with Western blotting. To explore the underlying mechanisms, VCAM-1 protein expression was also evaluated after activation of several signaling molecules including mitogen-activated protein kinases (MAPKs) and peroxisome proliferator-activated receptor γ (PPARγ) were blocked. Exposure of synovial cells to MSU crystals induced VCAM-1 expression in culture medium in a dose-and timedependent manner, reaching a plateau at 1000 µM and 24 h. Inhibition of the activation of MAPKs and PPARγ could block this increase. The present results demonstrated that MSU crystals could induce VCAM-1 expression. MAPKs and PPARγ signaling pathways regulated the induced VCAM-1 expression.