Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Junkins, Robert D.; MacNeil, Adam J.; Wu, Zhengli; McCormick, Craig; Lin, Tong‐Jun

doi:10.4049/jimmunol.1203196

Cited by 30 publications

(27 citation statements)

References 81 publications

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“…EMSA was performed using a 32 P-labled oligonucleotide probe specific for the NF-κB consensus sequence on the IL-6 promoter [57]. Briefly, 10 μg of nuclear protein was added to 10 μl of binding buffer supplemented with 1 μg poly-(dI-dC) (GE Healthcare) and incubated at room temperature for 15 minutes before mixing with the probe.…”

Section: Methodsmentioning

confidence: 99%

IL-17RC is critically required to maintain baseline A20 production to repress JNK isoform-dependent tumor-specific proliferation

Yan¹,

Lei

Lin

et al. 2017

Oncotarget

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The IL-17/IL-17R axis has controversial roles in cancer, which may be explained by tumor-specific results. Here, we describe a novel molecular mechanism underlying IL-17RC-controlled tumor-specific proliferation. Triggered by IL-17RC knockdown (KD), B16 melanoma and 4T1 carcinoma cells inversely altered homeostatic tumor proliferation and tumor growth in vitro and in vivo. In contrast to the existing dogma that IL-17RC-dependent signaling activates the JNK pathway, IL-17RC KD in both tumor cell lines caused aberrant expression and activation of different JNK isoforms along with markedly diminished levels of the ubiquitin-editing enzyme A20. We demonstrated that differential up-regulation of JNK1 and JNK2 in the two tumor cell lines was responsible for the reciprocal regulation of c-Jun activity and tumor-specific proliferation. Furthermore, we showed that A20 reconstitution of IL-17RCKD clones with expression of full-length A20, but not a truncation-mutant, reversed aberrant JNK1/JNK2 activities and tumor-specific proliferation. Collectively, our study reveals a critical role of IL-17RC in maintaining baseline A20 production and a novel role of the IL-17RC-A20 axis in controlling JNK isoform-dependent tumor-specific homeostatic proliferation.

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Section: Methodsmentioning

confidence: 99%

IL-17RC is critically required to maintain baseline A20 production to repress JNK isoform-dependent tumor-specific proliferation

Yan¹,

Lei

Lin

et al. 2017

Oncotarget

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“…As mentioned earlier, Down syndrome is associated with increased risk and severity of viral and bacterial pneumonias. RCAN1, encoded on Hsa21, regulates inflammatory responses to Pseudomonas infection both in vitro and in vivo [199]. Interestingly, dysregulation of NFAT, NF-κB and STAT3 signalling pathways was observed in the setting of RCAN1 deficiency.…”

Section: Genetic Influence Of Trisomy 21 On Immune System Disturbancementioning

confidence: 99%

What people with Down Syndrome can teach us about cardiopulmonary disease

Colvin

Yeager

2017

Eur Respir Rev

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Down syndrome is the most common chromosomal abnormality among live-born infants. Through full or partial trisomy of chromosome 21, Down syndrome is associated with cognitive impairment, congenital malformations ( particularly cardiovascular) and dysmorphic features. Immune disturbances in Down syndrome account for an enormous disease burden ranging from quality-of-life issues (autoimmune alopecia) to more serious health issues (autoimmune thyroiditis) and life-threatening issues (leukaemia, respiratory tract infections and pulmonary hypertension). Cardiovascular and pulmonary diseases account for ∼75% of the mortality seen in persons with Down syndrome. This review summarises the cardiovascular, respiratory and immune challenges faced by individuals with Down syndrome, and the genetic underpinnings of their pathobiology. We strongly advocate increased comparative studies of cardiopulmonary disease in persons with and without Down syndrome, as we believe these will lead to new strategies to prevent and treat diseases affecting millions of people worldwide.

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“…We then examined the involvement of NF-κB, a transcription factor that plays a crucial role in inflammation, immunity, cell proliferation and apoptosis (25)(26)(27)(28). NF-κB affected the LPS-induced E-selectin and ICAM-1 expression.…”

Section: Inhibition Of Mapk and Nf-κb Pathways Suppresses The Mrna Exmentioning

confidence: 99%

Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

Liu

Wei

et al. 2013

International Journal of Molecular Medicine

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Abstract. The expression of adhesion molecules in endothelial cells elicited by lipopolysaccharide (LPS) is involved in the adhesive interaction between endothelial cells and monocytes in inflammation. In this study, in order to characterize the anti-inflammatory effects of chitosan oligosaccharides (COS) on LPS-induced inflammation and to elucidate the underlying mechanisms, the mRNA levels of E-selectin and intercellular adhesion molecule-1 (ICAM-1) were measured in porcine iliac artery endothelial cells (PIECs). When these cells were treated with COS, the LPS-induced mRNA expression of E-selectin and ICAM-1 was reduced through the inhibition of the signal transduction cascade, p38 mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinase 1/2 (ERK1/2) and nuclear factor-κB (NF-κB). Moreover, through the inhibition of p38 MAPK and ERK1/2, COS suppressed the LPS-induced NF-κB p65 translocation. We found that COS suppressed the phosphorylation of p38 MAPK and the translocation of NF-κB p65 into the nucleus in a dose-dependent manner, and inhibited the adhesion of U973 cells to PIECs. Based on these results, it can be concluded that COS downregulate the expression of E-selectin and ICAM-1 by inhibiting the phosphorylation of MAPKs and the activation of NF-κB in LPS-treated PIECs. Our study demonstrates the valuable anti-inflammatory properties of COS. IntroductionChitosan oligosaccharides (COS), consisting of D-glucosamine linked via β-1,4-glycosides, are derived from chitosan by chemical or enzymatic hydrolysis (1). It has been reported that COS exhibit various biological activities, such as antitumor (2) and antioxidant properties (3), owing to their low molecular weight, high absorption, solubility and biocompatibility (4). In addition, recent studies have paid more attention to the regulatory role of COS in inflammatory responses (5,6).Lipopolysaccharide (LPS), the major component of the outer membrane of Gram-negative bacteria, can act as an endotoxin and initiates serious inflammatory responses in vitro and in vivo (7,8) by upregulating the expression of adhesion molecules and cytokines, such as E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and tumor necrosis factor-α (TNF-α) (9,10). Endothelial cells are the target of inflammatory responses and thereby, of a number of severe disorders, including sepsis and multiple organ dysfunctions that occur via LPS stimulation (11). In this study, we detected the expression of the adhesion molecules, E-selectin and ICAM-1 in LPS-treated porcine iliac artery endothelial cells (PIECs), since the upregulation of adhesion molecules and the increased secretion of cytokines and chemokines are known to occur during endothelial cell activation (12)(13)(14).The evolutionary conserved family of mitogen-activated protein kinases (MAPKs) includes extracellular p38 MAPK, extracellular regulated protein kinase (ERK) and c-Jun N-terminal kinase (JNK) (15). Numerous environmental stresses, such as osmotic shock, ...

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Regulator of Calcineurin 1 Suppresses Inflammation during Respiratory Tract Infections

Cited by 30 publications

References 81 publications

IL-17RC is critically required to maintain baseline A20 production to repress JNK isoform-dependent tumor-specific proliferation

IL-17RC is critically required to maintain baseline A20 production to repress JNK isoform-dependent tumor-specific proliferation

What people with Down Syndrome can teach us about cardiopulmonary disease

Chitosan oligosaccharides downregulate the expression of E-selectin and ICAM-1 induced by LPS in endothelial cells by inhibiting MAP kinase signaling

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