The Structure and Signaling Mechanisms of Type 1 Cytokine Receptors: A Brief Overview

ABSTRACT Mice of the PERA/Ei strain (PE mice) are highly susceptible to tumor induction by polyomavirus and transmit their susceptibility in a dominant manner in crosses with resistant C57BR/cdJ mice (BR mice). BR mice respond to polyomavirus infection with a type 1 cytokine response and develop effective cell-mediated immunity to the virus-induced tumors. By enumerating virus-specific CD8+ T cells and measuring cytokine responses, we show that the susceptibility of PE mice is due to the absence of a type 1 cytokine response and a concomitant failure to sustain virus-specific cytotoxic T lymphocytes. (PE × BR)F1 mice showed an initial type 1 response that became skewed toward type 2. Culture supernatants of splenocytes from infected PE mice stimulated in vitro contained high levels of interleukin-10 and no detectable gamma interferon, while those from BR mice showed the opposite pattern. Differences in the innate immune response to polyomavirus by antigen-presenting cells in PE mice and BR mice led to polarization of T-cell cytokine responses. Adherent cells from spleens of infected BR mice produced high levels of interleukin-12, while those from infected PE and F1 mice produced predominantly interleukin-10. PE and F1 mice infected by polyomavirus responded with increases in antigen-presenting cells expressing B7.2 costimulatory molecules, whereas BR mice responded with increased expression of B7.1. Administration of recombinant interleukin-12 along with virus resulted in partial protection of PE mice and provided complete protection against tumor development in F1 animals.

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Decreased frequency of HCV core-specific peripheral blood mononuclear cells with type 1 cytokine secretion in chronic hepatitis C

Journal of Hepatology ◽

10.1016/s0168-8278(99)80307-9 ◽

1999 ◽

Vol 31 (6) ◽

pp. 971-978 ◽

Cited By ~ 59

Author(s):

Martin Lechmann ◽

Rainer P Woitas ◽

Bettina Langhans ◽

Rolf Kaiser ◽

Hans Georg Ihlenfeldt ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis C ◽

Chronic Hepatitis C ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Type 1 Cytokine

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IL-12-Deficient Mice Are Defective in IFNγ Production and Type 1 Cytokine Responses

Immunity ◽

10.1016/s1074-7613(00)80413-6 ◽

1996 ◽

Vol 4 (5) ◽

pp. 471-481 ◽

Cited By ~ 713

Author(s):

Jeanne Magram ◽

Suzanne E Connaughton ◽

Rajeev R Warrier ◽

Daisy M Carvajal ◽

Chang-you Wu ◽

...

Keyword(s):

Cytokine Responses ◽

Type 1 Cytokine ◽

Deficient Mice

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Reconstruction of Protein-Protein Interaction Network of Insulin Signaling inHomo Sapiens

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/690925 ◽

2010 ◽

Vol 2010 ◽

pp. 1-7 ◽

Cited By ~ 5

Author(s):

Saliha Durmuş Tekir ◽

Pelin Ümit ◽

Aysun Eren Toku ◽

Kutlu Ö. Ülgen

Keyword(s):

Type 2 Diabetes ◽

Insulin Signaling ◽

Homo Sapiens ◽

Interaction Network ◽

Protein Protein Interaction ◽

Signaling Mechanisms ◽

Reconstructed Network ◽

Protein Protein Interaction Network

Diabetes is one of the most prevalent diseases in the world. Type 1 diabetes is characterized by the failure of synthesizing and secreting of insulin because of destroyed pancreaticβ-cells. Type 2 diabetes, on the other hand, is described by the decreased synthesis and secretion of insulin because of the defect in pancreaticβ-cells as well as by the failure of responding to insulin because of malfunctioning of insulin signaling. In order to understand the signaling mechanisms of responding to insulin, it is necessary to identify all components in the insulin signaling network. Here, an interaction network consisting of proteins that have statistically high probability of being biologically related to insulin signaling inHomo sapienswas reconstructed by integrating Gene Ontology (GO) annotations and interactome data. Furthermore, within this reconstructed network, interacting proteins which mediate the signal from insulin hormone to glucose transportation were identified using linear paths. The identification of key components functioning in insulin action on glucose metabolism is crucial for the efforts of preventing and treating type 2 diabetes mellitus.

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