A pathogenetic role for TNF alpha in the syndrome of cachexia, arthritis, and autoimmunity resulting from tristetraprolin (TTP) deficiency.

Abstract:

:Tristetraprolin (TTP) is a widely expressed potential transcription factor that contains two unusual CCCH zinc fingers and is encoded by the immediate-early response gene, Zfp-36. Mice made deficient in TTP by gene targeting appeared normal at birth, but soon manifested marked medullary and extramedullary myeloid hyperplasia associated with cachexia, erosive arthritis, dermatitis, conjunctivitis, glomerular mesangial thickening, and high titers of anti-DNA and antinuclear antibodies. Myeloid progenitors from these mice showed no increase in sensitivity to growth factors. Treatment of young TTP-deficient mice with antibodies to tumor necrosis factor alpha (TNF alpha) prevented the development of essentially all aspects of the phenotype. These results indicate a role for TTP in regulating TNF alpha synthesis, secretion, turnover, or action. TTP-deficient mice may serve as useful models of the autoimmune inflammatory state resulting from chronic effective TNF alpha excess.

journal_name

Immunity

journal_title

Immunity

authors

Taylor GA,Carballo E,Lee DM,Lai WS,Thompson MJ,Patel DD,Schenkman DI,Gilkeson GS,Broxmeyer HE,Haynes BF,Blackshear PJ

doi

10.1016/s1074-7613(00)80411-2

subject

Has Abstract

pub_date

1996-05-01 00:00:00

pages

445-54

issue

5

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(00)80411-2

journal_volume

4

pub_type

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