scholarly journals SHP2 promotes NETosis through ERK5 pathway and mediates the development of psoriasis

Author(s):  
Yang Sun ◽  
Yan Ding ◽  
Jiao Qu ◽  
Chenyang Zhang ◽  
Yuyu Zhu ◽  
...  

Psoriasis is a chronic inflammatory disease which infiltrated a large number of neutrophils among skin lesions. Here, we investigated the contribution of tyrosine phosphatase SHP2 in neutrophils, as well as its pathogenesis in psoriasis. We combined single-cell RNA sequencing with experimental verification to declare that SHP2 in neutrophils could promote the NETs formation through the ERK5 pathway, and resulted in the infiltration of inflammatory immune cells, which leads to psoriasis. Our study provides evidence for the role of SHP2 in NETosis in the progression of psoriasis, and SHP2 may be a potential therapeutic target for the treatment of psoriasis.

2021 ◽  
Vol 22 (13) ◽  
pp. 7227
Author(s):  
Lai-San Wong ◽  
Yu-Ta Yen ◽  
Chih-Hung Lee

Atopic dermatitis (AD) is a prototypic inflammatory disease that presents with intense itching. The pathophysiology of AD is multifactorial, involving environmental factors, genetic susceptibility, skin barrier function, and immune responses. A recent understanding of pruritus transmission provides more information about the role of pruritogens in the pathogenesis of AD. There is evidence that pruritogens are not only responsible for eliciting pruritus, but also interact with immune cells and act as inflammatory mediators, which exacerbate the severity of AD. In this review, we discuss the interaction between pruritogens and inflammatory molecules and summarize the targeted therapies for AD.


2021 ◽  
Vol 11 ◽  
Author(s):  
Manqiu Ding ◽  
Yongqiang Chen ◽  
Yue Lang ◽  
Li Cui

Prion protein has two isoforms including cellular prion protein (PrPC) and scrapie prion protein (PrPSc). PrPSc is the pathological aggregated form of prion protein and it plays an important role in neurodegenerative diseases. PrPC is a glycosylphosphatidylinositol (GPI)-anchored protein that can attach to a membrane. Its expression begins at embryogenesis and reaches the highest level in adulthood. PrPC is expressed in the neurons of the nervous system as well as other peripheral organs. Studies in recent years have disclosed the involvement of PrPC in various aspects of cancer biology. In this review, we provide an overview of the current understanding of the roles of PrPC in proliferation, cell survival, invasion/metastasis, and stem cells of cancer cells, as well as its role as a potential therapeutic target.


2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Iyad Khamaysi ◽  
Preeti Singh ◽  
Susan Nasser ◽  
Hoda Awad ◽  
Yehuda Chowers ◽  
...  

2020 ◽  
Vol 319 (3) ◽  
pp. R282-R287
Author(s):  
Maycon I. O. Milanez ◽  
Erika E. Nishi ◽  
Cássia T. Bergamaschi ◽  
Ruy R. Campos

The control of sympathetic vasomotor activity involves a complex network within the brain and spinal circuits. An extensive range of studies has indicated that sympathoexcitation is a common feature in several cardiovascular diseases and that strategies to reduce sympathetic vasomotor overactivity in such conditions can be beneficial. In the present mini-review, we present evidence supporting the spinal cord as a potential therapeutic target to mitigate sympathetic vasomotor overactivity in cardiovascular diseases, focusing mainly on the actions of spinal angiotensin II on the control of sympathetic preganglionic neuronal activity.


2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Fei Fei Guo ◽  
Jiu Wei Cui

Earlier studies on elucidating the role of lymphocytes in tumor immunity predominantly focused on T cells. However, the role of B cells in tumor immunity has increasingly received better attention in recent studies. The B cells that infiltrate tumor tissues are called tumor-infiltrating B cells (TIBs). It is found that TIBs play a multifaceted dual role in regulating tumor immunity rather than just tumor inhibition or promotion. In this article, latest research advances focusing on the relationship between TIBs and tumor complexity are reviewed, and light is shed on some novel ideas for exploiting TIBs as a possible tumor biomarker and potential therapeutic target against tumors.


Author(s):  
Esther Lutgens ◽  
Marie-Luce Bochaton-Piallat ◽  
Christian Weber

Atherosclerosis is a lipid-driven, chronic inflammatory disease of the large and middle-sized arteries that affects every human being and slowly progresses with age. The disease is characterized by the presence of atherosclerotic plaques consisting of lipids, (immune) cells, and debris that form in the arterial intima. Plaques develop at predisposed regions characterized by disturbed blood flow dynamics, such as curvatures and branch points. In the past decades, experimental and patient studies have revealed the role of the different cell-types of the innate and adaptive immune system, and of non-immune cells such as platelets, endothelial, and vascular smooth muscle cells, in its pathogenesis. This chapter highlights the roles of these individual cell types in atherogenesis and explains their modes of communication using chemokines, cytokines, and co-stimulatory molecules.


Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 587 ◽  
Author(s):  
Matilda Munksgaard Thorén ◽  
Katarzyna Chmielarska Masoumi ◽  
Cecilia Krona ◽  
Xiaoli Huang ◽  
Soumi Kundu ◽  
...  

New, effective treatment strategies for glioblastomas (GBMs), the most malignant and invasive brain tumors in adults, are highly needed. In this study, we investigated the potential of integrin α10β1 as a therapeutic target in GBMs. Expression levels and the role of integrin α10β1 were studied in patient-derived GBM tissues and cell lines. The effect of an antibody–drug conjugate (ADC), an integrin α10 antibody conjugated to saporin, on GBM cells and in a xenograft mouse model was studied. We found that integrin α10β1 was strongly expressed in both GBM tissues and cells, whereas morphologically unaffected brain tissues showed only minor expression. Partial or no overlap was seen with integrins α3, α6, and α7, known to be expressed in GBM. Further analysis of a subpopulation of GBM cells selected for high integrin α10 expression demonstrated increased proliferation and sphere formation. Additionally, siRNA-mediated knockdown of integrin α10 in GBM cells led to decreased migration and increased cell death. Furthermore, the ADC reduced viability and sphere formation of GBM cells and induced cell death both in vitro and in vivo. Our results demonstrate that integrin α10β1 has a functional role in GBM cells and is a novel, potential therapeutic target for the treatment of GBM.


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