Expression and regulation of chemokines in murine and human type 1 diabetes

Suparna A. Sarkar, Catherine E. Lee, Francisco Victorino, Tom T. Nguyen, Jay A. Walters, Adam Burrack, Jens Eberlein, Steven K. Hildemann, Dirk Homann

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

More than one-half of the ∼50 human chemokines have been associated with or implicated in the pathogenesis of type 1 diabetes, yet their actual expression patterns in the islet environment of type 1 diabetic patients remain, at present, poorly defined. Here, we have integrated a human islet culture system, murine models of virus-induced and spontaneous type 1 diabetes, and the histopathological examination of pancreata from diabetic organ donors with the goal of providing a foundation for the informed selection of potential therapeutic targets within the chemokine/receptor family. Chemokine (C-C motif) ligand (CCL) 5 (CCL5), CCL8, CCL22, chemokine (C-X-C motif) ligand (CXCL) 9 (CXCL9), CXCL10, and chemokine (C-X3-C motif) ligand (CX3CL) 1 (CX3CL1) were the major chemokines transcribed (in an inducible nitric oxide synthase-dependent but not nuclear factor-κB-dependent fashion) and translated by human islet cells in response to in vitro inflammatory stimuli. CXCL10 was identified as the dominant chemokine expressed in vivo in the islet environment of prediabetic animals and type 1 diabetic patients, whereas CCL5, CCL8, CXCL9, and CX3CL1 proteins were present at lower levels in the islets of both species. Of importance, additional expression of the same chemokines in human acinar tissues emphasizes an underappreciated involvement of the exocrine pancreas in the natural course of type 1 diabetes that will require consideration for additional type 1 diabetes pathogenesis and immune intervention studies.

Original languageEnglish (US)
Pages (from-to)436-446
Number of pages11
JournalDiabetes
Volume61
Issue number2
DOIs
StatePublished - Feb 1 2012

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Type 1 Diabetes Mellitus
Chemokines
Chemokine CX3CL1
Ligands
CXC Chemokines
Exocrine Pancreas
CC Chemokines
Chemokine Receptors
Nitric Oxide Synthase Type II
Islets of Langerhans
Pancreas
Tissue Donors
Viruses
Proteins
Therapeutics

Cite this

Sarkar, S. A., Lee, C. E., Victorino, F., Nguyen, T. T., Walters, J. A., Burrack, A., ... Homann, D. (2012). Expression and regulation of chemokines in murine and human type 1 diabetes. Diabetes, 61(2), 436-446. https://doi.org/10.2337/db11-0853

Expression and regulation of chemokines in murine and human type 1 diabetes. / Sarkar, Suparna A.; Lee, Catherine E.; Victorino, Francisco; Nguyen, Tom T.; Walters, Jay A.; Burrack, Adam; Eberlein, Jens; Hildemann, Steven K.; Homann, Dirk.

In: Diabetes, Vol. 61, No. 2, 01.02.2012, p. 436-446.

Research output: Contribution to journalArticle

Sarkar, SA, Lee, CE, Victorino, F, Nguyen, TT, Walters, JA, Burrack, A, Eberlein, J, Hildemann, SK & Homann, D 2012, 'Expression and regulation of chemokines in murine and human type 1 diabetes', Diabetes, vol. 61, no. 2, pp. 436-446. https://doi.org/10.2337/db11-0853
Sarkar SA, Lee CE, Victorino F, Nguyen TT, Walters JA, Burrack A et al. Expression and regulation of chemokines in murine and human type 1 diabetes. Diabetes. 2012 Feb 1;61(2):436-446. https://doi.org/10.2337/db11-0853
Sarkar, Suparna A. ; Lee, Catherine E. ; Victorino, Francisco ; Nguyen, Tom T. ; Walters, Jay A. ; Burrack, Adam ; Eberlein, Jens ; Hildemann, Steven K. ; Homann, Dirk. / Expression and regulation of chemokines in murine and human type 1 diabetes. In: Diabetes. 2012 ; Vol. 61, No. 2. pp. 436-446.
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