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Itch protein

Jarkko Mäntylä, Tuuli Thomander, Auli Hakulinen, Kaarina Kukkonen, Kati Palosuo, Helena Voutilainen, Anna Pelkonen, Paula Kauppi
INTRODUCTION: The standard care of severe food allergy in both adults and children means avoidance of allergens. In recent years promising results of oral immunotherapy (OIT) have been reported in children. In adults, information on OIT in severe food allergy is very limited. OBJECTIVE: We aimed to study if OIT is possible in adults. METHODS: We report OIT results in 10 adult patients with milk OIT, nine adult patients with peanut OIT, and four adult patients with egg OIT...
March 15, 2018: Immunity, Inflammation and Disease
Tetsuo Koshizuka, Takahiro Kobayashi, Ken Ishioka, Tatsuo Suzutani
Nedd4 is a family of ubiquitin E3 ligases that regulate numerous cellular processes. In this report, we showed that alpha- and beta-herpesviruses have membrane proteins that regulate the function of the Nedd4 family members. Although the homology search score was quite low, UL56 of herpes simplex virus type 1 and 2, ORF0 of varicella-zoster virus, UL42 of human cytomegalovirus, and U24 of human herpesvirus 6A, 6B, and 7 all possess at least one PPxY (PY) motif in their cytoplasmic domain, and are able to bind with Itch, a member of the Nedd4 family...
March 13, 2018: Scientific Reports
Yu-Na Im, Yu-Dong Lee, Jeong-Soo Park, Hae-Kyoung Kim, Suhn-Young Im, Hwa-Ryung Song, Hern-Ku Lee, Myung-Kwan Han
Many itch mediators activate G-protein coupled receptor (GPCR), and trigger itch via activation of GPCR-mediated signaling pathways. GPCRs are desensitized by G protein-coupled receptor kinases (GRKs). The aim of this study is to explore the role of GRKs in itch response and the linkage between GRKs and glutamine (Gln), an amino acid previously demonstrated as an itching reliever. Itch responses were evoked by histamine, chloroquine (CQ), and dinitrochlorobenzene (DNCB)-induced contact dermatitis (CD). Phosphorylation and protein expression were detected by immunofluorescent staining and Western blotting...
March 9, 2018: Journal of Investigative Dermatology
Bin Li, Xiao Han, Xin Ye, Jianbo Ni, Jianghong Wu, Juanjuan Dai, Zengkai Wu, Congying Chen, Rong Wan, Xingpeng Wang, Guoyong Hu
Leukotriene B4 (LTB4) is a potent chemoattractant and inflammatory mediator involved in multiple inflammatory diseases. Substance P (SP) has been reported to promote production of LTB4 in itch-associated response in vivo and in some immune cells in vitro. Here, we investigated the role of LTB4 in acute pancreatitis (AP), AP-associated acute lung injury (ALI) and the related mechanisms of LTB4 production in AP. In vivo, murine AP model was induced by caerulein and lipopolysaccharide or L-arginine. The levels of LTB4 and its specific receptor BLT1 were markedly upregulated in both AP models...
February 23, 2018: International Immunopharmacology
Tiam M Saffari, Barthold N Schüttenhelm, Johan W van Neck, Jan C Holstege
In this study, we investigated whether post-burn itch in rats, after a full thickness burn, is correlated to the nervous reinnervation of the burn wound area. For this purpose, we determined scratching duration (expressed as sec/hr) at 24 hours, 2, 4, 8 and 12 weeks post-burn and combined this with immunohistochemistry for protein gene product 9.5 (PGP9.5) to identify all nerve fibers, calcitonin gene related peptide (CGRP) to identify peptidergic fibers, tyrosine hydroxylase (TH) for sympathetic fibers and growth-associated protein 43 (GAP-43) for regrowing fibers...
February 17, 2018: Wound Repair and Regeneration
Martin Steinhoff, Jörg Buddenkotte, Ethan A Lerner
To protect our body systems, there is a constant interactive conversation between the skin nervous and immune system. Important elements of this conversation in the skin include mast cells, basophils, and sensory nerve fibers. These cells employ a vast array of sensors that detect danger and react accordingly. This reaction, summarized as neurogenic inflammation, manifests at the conscious level as sensations including pain and itch. Here we provide a perspective on the blossoming knowledge that is illuminating connections between mast cells, basophils, and sensory nerve fibers in the mediation of itch...
March 2018: Immunological Reviews
Jiantao Xiao, Qing Shi, Weiguo Li, Xingyu Mu, Jintao Peng, Mingzi Li, Mulin Chen, Huabing Huang, Chenji Wang, Kun Gao, Jie Fan
The α-arrestins domain-containing 1 and 3 (ARRDC1 and ARRDC3) are two members of the α-arrestins family. Yes-associated protein 1 (YAP1) is a key downstream transcription co-activator of the Hippo pathway essential for cancer initiation, progression, or metastasis in clear cell renal cell carcinoma (ccRCC). The aim of this work was to elucidate the role of the α-arrestins in ccRCC tumorigenesis by identifying molecular interacting factors and exploring potential mechanisms. In this study, we identified YAP1 as a novel ARRDC3 interacting protein in RCC cells through tandem affinity purification and mass spectrometry...
2018: American Journal of Cancer Research
Chengdi Yang, Wenbo Yuan, Xiao Yang, Peng Li, Jingzi Wang, Jie Han, Jun Tao, Pengchao Li, Haiwei Yang, Qiang Lv, Wei Zhang
BACKGROUND: Circ-ITCH is a circRNA generated from several exons of itchy E3 ubiquitin protein ligase (ITCH) and tumor suppressor served as a sponge for certain miRNAs targeting their parental transcripts of ITCH. However, the role of circ-ITCH in bladder cancer (BCa) was not reported. In the present study, we investigated the role of circ-ITCH in BCa. METHODS: Quantitative real-time PCR was used to detect the expression of circ-ITCH and survival analysis was adopted to explore the association between circ-ITCH expression and the prognosis of BCa...
January 31, 2018: Molecular Cancer
Miguel Ortíz-Rentería, Rebeca Juárez-Contreras, Ricardo González-Ramírez, León D Islas, Félix Sierra-Ramírez, Itzel Llorente, Sidney A Simon, Marcia Hiriart, Tamara Rosenbaum, Sara L Morales-Lázaro
The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain...
February 13, 2018: Proceedings of the National Academy of Sciences of the United States of America
Tomoya Shingaki, Yukiko Hiraguchi, Mari Gen, Shoko Yoshino, Yusuke Kumagai, Yuko Ebishima, Kenji Owa, Kenta Otuji, Yasuto Kondou, Yutaka Suehiro
We experienced a case of 10-year-old girl who developed hypersensitivity reactions after eating enokitake. The patient had food allergy to egg until 5 years old. When she was 4 years old, she ate enokitake with a hot-pot dish. Later, she felt itching in her mouth. Therefore, she never ate enokitake since that time. At the age of 10, she drank only the soup of enokitake with school lunch. After that she felt discomfort and itching in her oral cavity. The result of enokitake and other mushrooms (siitake, simeji, and eringi) skin prick to prick test were all positive...
2017: Arerugī, [Allergy]
Anupama Pal, Michele Dziubinski, Marina Pasca Di Magliano, Diane M Simeone, Scott Owens, Dafydd Thomas, Luke Peterson, Harish Potu, Moshe Talpaz, Nicholas J Donato
Usp9x has emerged as a potential therapeutic target in some hematologic malignancies and a broad range of solid tumors including brain, breast, and prostate. To examine Usp9x tumorigenicity and consequence of Usp9x inhibition in human pancreatic tumor models, we carried out gain- and loss-of-function studies using established human pancreatic tumor cell lines (PANC1 and MIAPACA2) and four spontaneously immortalized human pancreatic patient-derived tumor (PDX) cell lines. The effect of Usp9x activity inhibition by small molecule deubiquitinase inhibitor G9 was assessed in 2D and 3D culture, and its efficacy was tested in human tumor xenografts...
December 14, 2017: Neoplasia: An International Journal for Oncology Research
Katharina Essig, Desheng Hu, Joao C Guimaraes, Dominik Alterauge, Stephanie Edelmann, Timsse Raj, Jan Kranich, Gesine Behrens, Alexander Heiseke, Stefan Floess, Juliane Klein, Andreas Maiser, Susan Marschall, Martin Hrabĕ de Angelis, Heinrich Leonhardt, Cornelis F Calkhoven, Elfriede Noessner, Thomas Brocker, Jochen Huehn, Anne B Krug, Mihaela Zavolan, Dirk Baumjohann, Vigo Heissmeyer
Roquin proteins preclude spontaneous T cell activation and aberrant differentiation of T follicular helper (Tfh) or T helper 17 (Th17) cells. Here we showed that deletion of Roquin-encoding alleles specifically in regulatory T (Treg) cells also caused the activation of conventional T cells. Roquin-deficient Treg cells downregulated CD25, acquired a follicular Treg (Tfr) cell phenotype, and suppressed germinal center reactions but could not protect from colitis. Roquin inhibited the PI3K-mTOR signaling pathway by upregulation of Pten through interfering with miR-17∼92 binding to an overlapping cis-element in the Pten 3' UTR, and downregulated the Foxo1-specific E3 ubiquitin ligase Itch...
December 19, 2017: Immunity
Giovanni Vitale, Stefano Gitto, Francesco Raimondi, Alessandro Mattiaccio, Vilma Mantovani, Ranka Vukotic, Antonietta D'Errico, Marco Seri, Robert B Russell, Pietro Andreone
BACKGROUND: Mutations in ATP-transporters ATPB81, ABCB11, and ABCB4 are responsible for progressive familial intrahepatic cholestasis (PFIC) 1, 2 and 3, and recently the gene for tight junction protein-2 (TJP2) has been linked to PFIC4. AIM: As these four genes have been poorly studied in young people and adults, we investigated them in this context here. METHODS: In patients with cryptogenic cholestasis, we analyzed the presence of mutations by high-throughput sequencing...
December 13, 2017: Journal of Gastroenterology
Jessica M Perez, Yinghua Chen, Tsan S Xiao, Derek W Abbott
Heightened and extended inflammation underlies the pathogenesis of many disorders, including inflammatory bowel disease, sepsis, and inflammatory arthritis. Ubiquitin networks help dictate the strength and duration of inflammatory signaling. In innate immunity, the itchy E3 ubiquitin protein ligase (ITCH)-A20 ubiquitin-editing complex inhibits receptor-interacting Ser/Thr kinase (RIPK) activation by removing Lys-63-linked polyubiquitinated chains from key proteins in the nuclear factor kappa B (NF-κB) signaling pathway...
January 19, 2018: Journal of Biological Chemistry
James Meixiong, Xinzhong Dong
Chronic, persistent itch is a devastating symptom that causes much suffering. In recent years, there has been great progress made in understanding the molecules, cells, and circuits underlying itch sensation. Once thought to be carried by pain-sensing neurons, itch is now believed to be capable of being transmitted by dedicated sensory labeled lines. Members of the Mas-related G protein-coupled receptor (Mrgpr) family demarcate an itch-specific labeled line in the peripheral nervous system. In the spinal cord, the expression of other proteins identifies additional populations of itch-dedicated sensory neurons...
November 27, 2017: Annual Review of Genetics
Roge M Navarro, Ander Pino, Asunción Martinez-Andres, Consuelo Molina, Ana María Martinez, Nahikari Martinez, Gorka Orive, Eduardo Anitua
BACKGROUND: Hair transplant surgery using follicular unit extraction technique (FUE) is a common surgical procedure for the treatment of severe hair loss. Blood-derived autologous growth factors have also proved to promote hair regeneration in patients with different types of alopecia. AIMS: The aim of this study was to evaluate the safety and clinical efficacy of plasma rich in growth factors (PRGF) technology as an adjuvant therapy for FUE surgery in hair loss affected patients...
October 26, 2017: Journal of Cosmetic Dermatology
Peter Dong, Changxiong Guo, Shengxiang Huang, Minghong Ma, Qin Liu, Wenqin Luo
The detection of pruritic (itchy) stimuli is mediated by a variety of receptors and channels expressed by primary sensory neurons. The G protein-coupled receptor (GPCR) MRGPRD is selectively expressed by a subset of mouse non-peptidergic nociceptors and functions as the molecular receptor for the itch-inducing chemical β-alanine. However, the channels responsible for generating electrical signals downstream of MRGPRD remain unclear. Here, we found that a member of the canonical TRP channel family, TRPC3, is highly expressed in MRGPRD(+) non-peptidergic nociceptors, raising the possibility of whether TRPC3 functions as a downstream channel in the MRGPRD signaling pathway...
October 24, 2017: Scientific Reports
Hao Shi, Guang Yu, Xiao Geng, Leying Gu, Niuniu Yang, Changming Wang, Chan Zhu, Yan Yang, Lei Yu, Danyou Hu, Xiaolin Yuan, Lei Lan, Guanyi Wu, Zongxiang Tang
Chronic itch, a distressing symptom of many cutaneous and systemic diseases, significantly impairs quality of life. However, its underlying molecular mechanism is still unclear. Mas-related G protein-coupled receptor A3 (MrgprA3) is considered an itch-specific receptor. MrgprA3 neurons are identified as a class of itch-specific neurons, but the role of MrgprA3 in chronic itch remains elusive. An acetone-ether-water (AEW) model as a histamine-independent itch model is often used in the study of chronic pruritus...
December 6, 2017: Neuroreport
Matthew L Lazenka, Megan J Moerke, E Andrew Townsend, Kevin B Freeman, F Ivy Carroll, S Stevens Negus
RATIONALE: Nalfurafine is a G protein signaling-biased kappa opioid receptor (KOR) agonist approved in Japan for second-line treatment of uremic pruritus. Neither nalfurafine nor any other KOR agonist is currently approved anywhere for treatment of pain, but recent evidence suggests that G protein signaling-biased KOR agonists may have promise as candidate analgesics/antipruritics with reduced side effects compared to nonbiased or ß-arrestin-signaling-biased KOR agonists. OBJECTIVES: This study compared nalfurafine effects in rats using assays of pain-stimulated and pain-depressed behavior used previously to evaluate other candidate analgesics...
October 24, 2017: Psychopharmacology
Amiko Hakuta, Yukie Yamaguchi, Tomoko Okawa, Shoko Yamamoto, Yasuo Sakai, Michiko Aihara
BACKGROUND: Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease in which type 2 allergic inflammation plays an important role. Collagen tripeptide (CTP) is a functional collagen fraction with a high content of Gly-X-Y tripeptides. OBJECTIVE: To examine the effect of CTP on inflammation in AD. METHODS: Levels of inflammatory cytokines and chemokines, such as thymus- and activation-regulated chemokine (TARC), macrophage-derived chemokine, and thymic stromal lymphopoietin (TSLP), were examined in human keratinocytes supplemented with or without CTP under AD-like inflammation...
September 28, 2017: Journal of Dermatological Science
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