IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils

Didichenko, Svetlana A; Spiegl, Nicole; Brunner, Thomas; Dahinden, Clemens A (2008). IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils. Blood, 112(10), pp. 3949-58. Washington, D.C.: American Society of Hematology 10.1182/blood-2008-04-149419

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The contribution of basophils in allergic disease and other Th2-type immune responses depends on their persistence at sites of inflammation, but the ligands and molecular pathways supporting basophil survival are largely unknown. The comparison of rates of apoptosis and of the expression of antiapoptotic proteins in different human granulocyte types revealed that basophils have a considerably longer spontaneous life span than neutrophils and eosinophils consistent with high levels of constitutive Bcl-2 expression. Interleukin-3 (IL-3) is the only ligand that efficiently protects basophils from apoptosis as evidenced by screening a large number of stimuli. IL-3 up-regulates the expression of the antiapoptotic proteins cIAP2, Mcl-1, and Bcl-X(L) and induces a rapid and sustained de novo expression of the serine/threonine kinase Pim1 that closely correlates with cytokine-enhanced survival. Inhibitor studies and protein transduction of primary basophils using wild-type and kinase-dead Pim1-Tat fusion-proteins demonstrate the functional importance of Pim1 induction in the IL-3-enhanced survival. Our data further indicate that the antiapoptotic Pim1-mediated pathway operates independently of PI3-kinase but involves the activation of p38 MAPK. The induction of Pim1 leading to PI3-kinase-independent survival as described here for basophils may also be a relevant antiapoptotic mechanism in other terminally differentiated leukocyte types.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute for Immunology (discontinued)

UniBE Contributor:

Brunner, Thomas and Dahinden, Clemens A.

ISSN:

0006-4971

ISBN:

18768389

Publisher:

American Society of Hematology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 15:02

Last Modified:

04 May 2014 23:19

Publisher DOI:

10.1182/blood-2008-04-149419

PubMed ID:

18768389

Web of Science ID:

000260691300011

URI:

https://boris.unibe.ch/id/eprint/27080 (FactScience: 101695)

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