Neuropoietic cytokines and activin A differentially regulate the phenotype of cultured sympathetic neurons
A number of cytokines sharing limited sequence homology have been grouped as a family because of partially overlapping biological activities, receptor subunit promiscuity, and the prediction of a shared secondary structure. Since several of these cytokines regulate gene expression and cell number in the nervous and hematopoietic systems, this specific group is termed the neuropoietic cytokine family. Using a reverse transcription-polymerase chain reaction-based assay system for monitoring the expression of multiple phenotypic markers in cultured sympathetic neurons, we present further evidence that, in addition to cholinergic differentiation factor/leukemia inhibitory factor and ciliary neurotrophic factor, oncostatin M, growth promoting activity, interleukin 6, and interleukin 11 belong in this family. In addition, one member of the transforming growth factor beta superfamily, activin A, shares a selective overlap with the neuropoietic family in the spectrum of neuropeptides that it induces in sympathetic neurons. The particular neuropeptides induced by activin A, however, demonstrate that the activity of this cytokine is distinct from that of the neuropoietic family. Twenty-six other cytokines and growth factors were without detectable activity in this assay.
Copyright © 1994 by the National Academy of Sciences. Communicated by Norman Davidson, August 31, 1993 (received for review July 2, 1993). We thank Doreen McDowell for help with tissue culture materials and Drs. James Miller, Rae Nishi, Jim Smith, David Shelton, David Gearing, Yu-Chung Yang, Stanley Wolf, Mary Freshney, and Gerry Graham for providing cytokines. We are grateful to Dr. Rae Nishi for providing information concerning GPA and activin A activities before publication. We thank Drs. Lisa Banner, Herman Govan, Zaven Kaprielian, and Manhendra Rao and two reviewers for constructive comments on the manuscript. This project is supported by grants from Amgen and the National Institute of Neurological Disorders and Stroke (Javits Neuroscience Investigator Award) to P.H.P., as well as a Fellowship from the Ministry of Education, Taiwan, Republic of China, to M.-J.F. The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.
Published - FANpnas94.pdf