Author
Blair R. Renshaw
Bio: Blair R. Renshaw is an academic researcher from Amgen. The author has contributed to research in topics: Interleukin & Receptor. The author has an hindex of 14, co-authored 21 publications receiving 2452 citations.
Topics: Interleukin, Receptor, Orphan receptor, Jurkat cells, Kinase
Papers
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TL;DR: Aberrant interleukin-36Ra structure and function lead to unregulated secretion of inflammatory cytokines and generalized pustular psoriasis.
Abstract: Background Generalized pustular psoriasis is a life-threatening disease of unknown cause. It is characterized by sudden, repeated episodes of high-grade fever, generalized rash, and disseminated pustules, with hyperleukocytosis and elevated serum levels of C-reactive protein, which may be associated with plaque-type psoriasis. Methods We performed homozygosity mapping and direct sequencing in nine Tunisian multiplex families with autosomal recessive generalized pustular psoriasis. We assessed the effect of mutations on protein expression and conformation, stability, and function. Results We identified significant linkage to an interval of 1.2 megabases on chromosome 2q13-q14.1 and a homozygous missense mutation in IL36RN, encoding an interleukin-36–receptor antagonist (interleukin-36Ra), an antiinflammatory cytokine. This mutation predicts the substitution of a proline residue for leucine at amino acid position 27 (L27P). Homology-based structural modeling of human interleukin-36Ra suggests that the proli...
787 citations
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TL;DR: It is demonstrated that IL-1F6 and IL- 1F8, in addition to IL-2F9, activate the pathway leading to NF-κB in an IL-3Rrp2-dependent manner in Jurkat cells as well as in multiple other human and mouse cell lines, and thatIL-1RrP2 antibodies block activation of the pathwayLeading to NF -κB by IL-0F6, IL-8, and Il-1
395 citations
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TL;DR: The cloning and characterization of four new members of the interleukin-1 (IL-1) family (FIL1δ, FIL1ε, Fil1ζ, and FIL1η, with FIL1 standing for “Family of IL-1”) are reported here.
351 citations
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TL;DR: It is demonstrated that IL-36Ra antagonist activity is dependent upon removal of its N-terminal methionine, and the mechanism of action is directly analogous to that of IL-1Ra, which suggests that protease(s) that activate IL- 36 cytokines could be excellent drug targets for psoriasis.
278 citations
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TL;DR: It is concluded that the SIGIRR protein represents a novel subtype of the IL-1R superfamily, which has only one Ig domain in its extracellular portion and an unusually long cytoplasmic domain is reminiscent of the structure of drosophila Toll.
192 citations
Cited by
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TL;DR: An overview of established NF-kappaB signaling pathways is provided with focus on the current state of research into the mechanisms that regulate IKK activation and NF- kappaB transcriptional activity.
Abstract: The transcription factor NF-kappaB has been the focus of intense investigation for nearly two decades. Over this period, considerable progress has been made in determining the function and regulation of NF-kappaB, although there are nuances in this important signaling pathway that still remain to be understood. The challenge now is to reconcile the regulatory complexity in this pathway with the complexity of responses in which NF-kappaB family members play important roles. In this review, we provide an overview of established NF-kappaB signaling pathways with focus on the current state of research into the mechanisms that regulate IKK activation and NF-kappaB transcriptional activity.
3,829 citations
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TL;DR: A member of theIL-1 family, IL-33, which mediates its biological effects via IL-1 receptor ST 2, activates NF-kappaB and MAP kinases, and drives production of T(H)2-associated cytokines from in vitro polarized T( H)2 cells is reported.
3,306 citations
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TL;DR: The IL-1 family includes members that suppress inflammation, both specifically within the IL-2 family but also nonspecifically for TLR ligands and the innate immune response.
Abstract: More than any other cytokine family, the interleukin (IL)-1 family is closely linked to the innate immune response. This linkage became evident upon the discovery that the cytoplasmic domain of the IL-1 receptor type I is highly homologous to the cytoplasmic domains of all Toll-like receptors (TLRs). Thus, fundamental inflammatory responses such as the induction of cyclooxygenase type 2, increased expression of adhesion molecules, or synthesis of nitric oxide are indistinguishable responses of both IL-1 and TLR ligands. Both families nonspecifically affect antigen recognition and lymphocyte function. IL-1β is the most studied member of the IL-1 family because of its role in mediating autoinflammatory diseases. Although the TLR and IL-1 families evolved to assist in host defense against infection, unlike the TLR family, the IL-1 family also includes members that suppress inflammation, both specifically within the IL-1 family but also nonspecifically for TLR ligands and the innate immune response.
3,032 citations
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TL;DR: The identification of molecules that modulate the release of NETs has helped to refine the view of the role of neutrophils in immune protection, inflammatory and autoimmune diseases and cancer.
Abstract: Neutrophils are innate immune phagocytes that have a central role in immune defence. Our understanding of the role of neutrophils in pathogen clearance, immune regulation and disease pathology has advanced dramatically in recent years. Web-like chromatin structures known as neutrophil extracellular traps (NETs) have been at the forefront of this renewed interest in neutrophil biology. The identification of molecules that modulate the release of NETs has helped to refine our view of the role of NETs in immune protection, inflammatory and autoimmune diseases and cancer. Here, I discuss the key findings and concepts that have thus far shaped the field of NET biology.
1,564 citations
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TL;DR: The key properties of IL-1 family members are reviewed, with emphasis on pathways of negative regulation and orchestration of innate and adaptive immunity.
1,545 citations