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A sweat gland-derived differentiation activity acts through known cytokine signaling pathways

B A Habecker1, A J Symes, N Stahl

  • 1Department of Neurosciences, Case Western Reserve University, Cleveland, Ohio 44106, USA.

The Journal of Biological Chemistry
|December 31, 1997
PubMed

Insights

Sweat gland cells induce developmental changes in sympathetic neurons. This activity utilizes the same signaling pathway as neuropoietic cytokines, suggesting it is a related family member.

Area of Science:

  • Neuroscience
  • Developmental Biology
  • Cell Signaling

Background:

  • Sympathetic innervation of sweat glands switches from noradrenergic to cholinergic/peptidergic during development.
  • This switch can be mimicked by sweat gland cells or specific cytokines like leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), and cardiotrophin-1 (CT-1).
  • These cytokines signal through LIF receptor beta (LIFRbeta) and gp130, activating pathways like STAT3.

Purpose of the Study:

  • To determine if the sweat gland-derived differentiation activity belongs to the LIF/CNTF cytokine family.
  • To investigate if this activity utilizes the same receptors and signaling pathways as known neuropoietic cytokines.

Main Methods:

  • Neuron/gland co-cultures were used to assess sweat gland differentiation activity.
  • LIFRbeta blockade was employed to inhibit differentiation.
  • Tyrosine phosphorylation of LIFRbeta and gp130 was measured in response to footpad extracts.
  • NBFL neuroblastoma cells were treated with footpad extracts to analyze changes in vasoactive intestinal peptide (VIP) mRNA, STAT3 dimerization, DNA binding, and transcription.

Main Results:

  • Blocking LIFRbeta inhibited sweat gland differentiation activity in co-cultures.
  • Footpad extracts stimulated tyrosine phosphorylation of LIFRbeta and gp130.
  • An inhibitor of CNTFRalpha did not affect the gland-derived activity, differentiating it from CNTF signaling.
  • Footpad extracts induced VIP mRNA expression, STAT3 activation, and transcription in NBFL cells, mirroring LIF and CNTF effects.

Conclusions:

  • The sweat gland-derived differentiation activity shares the signaling pathway with neuropoietic cytokines.
  • This suggests the sweat gland factor is likely a member of the LIF/CNTF cytokine family.
  • This finding provides insight into the molecular mechanisms regulating sympathetic nerve development and function in sweat glands.

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