Neonates are extremely susceptible to bacterial infections, and evidences suggest that phagocytosis-induced cell death (PICD) is less frequently triggered in neonatal monocytes than in monocytes from adult donors. An insufficient termination of the inflammatory response, leading to a prolonged survival of neonatal monocytes with ongoing proinflammatory cytokine release, could be associated with the progression of various inflammatory diseases in neonates. Our previous data indicate that amphiregulin (AREG) is increasingly expressed on the cell surface of neonatal monocytes, resulting in remarkably higher soluble AREG levels after proteolytic shedding. In this study, we found that E. coli-infected neonatal monocytes show an increased phosphorylation of ERK, increased expression of Bcl-2 and Bcl-XL, and reduced levels of cleaved caspase-3 and caspase-9 compared to adult monocytes. In both cell types, additional stimulation with soluble AREG further increased ERK activation and expression of Bcl-2 and Bcl-XL and reduced levels of cleaved caspase-3 and caspase-9 in an EGFR-dependent manner. These data suggest that reduced PICD of neonatal monocytes could be due to reduced intrinsic apoptosis and that AREG can promote protection against PICD. This reduction of the intrinsic apoptosis pathway in neonatal monocytes could be relevant for severely prolonged inflammatory responses of neonates.
Neonates are highly susceptible to microbial infections which is partially attributable to fundamental phenotypic and functional differences between effector cells of the adult and neonatal immune system. The resolution of the inflammation is essential to return to tissue homeostasis, but given that various neonatal diseases, such as periventricular leukomalacia, necrotizing enterocolitis, or bronchopulmonary dysplasia, are characterized by sustained inflammation, newborns seem predisposed to a ...
Last. Tong-Xin Chen(SJTU: Shanghai Jiao Tong University)H-Index: 12
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Background The uncontrolled inflammatory response following infection is closely related to the morbidity and mortality of neonates. Interleukin 6 (IL-6) plays an important role in the pathogenesis and prognosis of this process. To better elucidate the secretion of IL-6 following infection in neonates, we investigated the IL-6 level and mechanism of IL-6/TLR4 signaling pathways. Methods We compared the IL-6, procalcitonin (PCT), and CRP levels between septic neonates and toddlers. In vitro cord ...
Last. Lu Xu(SJTU: Shanghai Jiao Tong University)H-Index: 6
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// Ling Li 1, * , Xiajing Gu 1, * , Jinnan Yue 1 , Qingnan Zhao 1 , Dacheng Lv 1 , Hongzhuan Chen 1 and Lu Xu 1 1 Department of Pharmacology, Shanghai Jiao Tong University School of Medicine, Shanghai, China * These authors have contributed equally to this work Correspondence to: Lu Xu, email: luxuluxu@yahoo.com Hongzhuan Chen, email: hongzhuan_chen@hotmail.com Keywords: EMT, IGF1R, NF-κB, NSCLC, EGFR TKI resistance Received: April 07, 2017 Accepted: August 26, 2017 Published: September 21, 2017...
Last. Jiahong Xia(HUST: Huazhong University of Science and Technology)H-Index: 12
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Abstract Previous studies mainly focused on the role of Epidermal growth factor receptor (EGFR) in tumor cells, while the effects of EGFR on immune responses has not been determined. Our study shown that EGFR signaling pathway play a role in regulation of Treg cells in cancer patients. The EGF-like growth factor Amphiregulin (AREG) protein was frequently upregulated in tissue microarray and in sera, tissue specimen and effusion of lung cancer and gastric cancer patients and upregulated AREG prot...
// Shuqing Li 1 * , Lina Yang 1 * , Jingshu Wang 1 , Fan Liang 1 , Bin Chang 2 , Huafen Gu 1 , Honglin Wang 1 , Gong Yang 3, 4 , Yaping Chen 1 1 Department of Obstetrics and Gynecology, The Fifth People’s Hospital of Shanghai, Fudan University, Shanghai 200240, China 2 Department of Pathology, Fudan University Shanghai Cancer Center, and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China 3 Cancer Institute, Fudan University Shanghai Cancer Center, and Depa...
Last. Inae Park(SNU: Seoul National University)H-Index: 1
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Purpose Human epidermal growth factor receptor 2 (HER2) heterodimerizes and shares common signaling pathways with epidermal growth factor receptor (EGFR). In this study, we investigated the clinical implication of amphiregulin, a ligand for EGFR, on trastuzumab therapy in HER2-positive breast cancer.
Last. Zhuo Zhang(The Graduate Center, CUNY)H-Index: 51
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Hexavalent chromium (Cr(VI)) compounds are well-established lung carcinogens. Epidermal growth factor receptor (EGFR) is a tyrosine kinase transmembrane receptor that regulates cell survival, tumor invasion, and angiogenesis. Our results show that chronic exposure of human bronchial epithelial (BEAS-2B) cells to Cr(VI) is able to cause malignant cell transformation. These transformed cells exhibit apoptosis resistance with reduced poly ADP-ribose polymerase cleavage (C-PARP) and Bax expression a...
Bax, a pro-apoptotic member of the Bcl-2 family of proteins has the ability to form transmembrane pores large enough to allow cytochrome c (Cyt c) release, as well as to activate the mitochondrial permeability transition pore (mPTP); however, no differential study has been conducted to clarify which one of these mechanisms predominates over the other in the same system. In the present study, we treated isolated mitochondria from MCF7 cells with recombinant protein Bax and tested the efficacy of ...
The BCL-2 homolog BCL-XL, one of the two protein products of BCL2L1, has originally been characterized for its prominent prosurvival functions. Similar to BCL-2, BCL-XL binds to its multidomain proapoptotic counterparts BAX and BAK, hence preventing the formation of lethal pores in the mitochondrial outer membrane, as well as to multiple BH3-only proteins, thus interrupting apical proapoptotic signals. In addition, BCL-XL has been suggested to exert cytoprotective functions by sequestering a cyt...
Gaucher disease (GD) is an autosomal recessive disorder caused by bi-allelic GBA1 mutations that reduce the activity of the lysosomal enzyme β-glucocerebrosidase (GCase). GCase catalyzes the conversion of glucosylceramide (GluCer), a ubiquitous glycosphingolipid, to glucose and ceramide. GCase deficiency causes the accumulation of GluCer and its metabolite glucosylsphingosine (GluSph) in a number of tissues and organs. In the immune system, GCase deficiency deregulates signal transduction events...
MΦ differentiate from circulating monocytes (Mo). The reduced ability of neonatal Mo to undergo apoptosis after E. coli infection (phagocytosis-induced cell death (PICD)) could contribute to sustained inflammatory processes. The objective of our study was to investigate whether immune metabolism in Mo can be modified to gain access to pro-apoptotic signaling. To this end, we supplemented Mo from neonates and from adults with the branched amino acid leucine. In neonatal Mo, we observed increased ...
#2Jingrou Chen(SYSU: Sun Yat-sen University)H-Index: 1
Last. Yanwen Peng(SYSU: Sun Yat-sen University)H-Index: 16
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OBJECTIVES Amphiregulin (Areg), a glycoprotein from the epidermal growth factor receptor (EGFR) ligand family, has a well-documented protective role against tissue injury; however, its effects on immune-mediated liver injury are still unclear. Here, we used a concanavalin A (ConA)-induced acute liver hepatitis model to explore the effects of Areg on immune-mediated acute liver injury. MATERIALS AND METHODS Some C57BL/6 mice were administered ConA at a dose of 20 mg/kg (model mice), and some rece...
