Neuromodulatory loop mediated by nerve growth factor and interleukin 6 in thymic stromal cell cultures.
Neural crest cell derivatives have been suggested to be involved in thymus development. We established nonlymphoid thymic stromal cell cultures capable of supporting T-cell differentiation. In these nonlymphoid cell cultures, we identified cells with phenotypic and biochemical markers specific for neuronal cells. Neurofilament mRNA and 68- and 160-kDa neurofilament proteins, as well as 74-kDa synapsin I isoform, were expressed in many of the cultured cells. For example, neurofilament immunoreactivity was detected in 20-30% of the cells. To see whether thymic neuronal-like cells were involved in a neural differentiation pathway, we investigated the effect of nerve growth factor (NGF) and interleukin 6 (IL-6), two known neurotrophic factors. The expression of the above-described neural markers was enhanced by NGF and IL-6, which we report to be produced in an autocrine way by thymic stromal cell cultures. Finally, we found that IL-6 gene expression in these cell cultures was enhanced by NGF. Evidence is thus offered of a neuromodulatory loop within the thymic stromal cell population supported by local production of NGF and IL-6 and involving neural cell elements. Interestingly, IL-6, which is known to be implicated in thymocyte differentiation, also displays a neuromodulatory activity on thymic stromal cells, suggesting a multivalent role for this cytokine within the thymus.
Genoa National Institute for Cancer Research, Biotechnology Section, Rome, Italy.
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I
Screpanti
D
D
Meco
S
S
Scarpa
S
S
Morrone
L
L
Frati
A
A
Gulino
A
A
Modesti
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004848:Epithelium / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016900:Neurofilament Proteins / Q000235:genetics*; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016704:Synapsins / Q000235:genetics; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
D015850:Interleukin-6; D009414:Nerve Growth Factors; D016900:Neurofilament Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016704:Synapsins; D012313:RNA