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Substance P activates both inflammatory and contractile signaling pathways in the lymphatics through neurokinin receptors
Author(s) -
Chakraborty Sanjukta,
Wang Wei,
Zawieja David C,
Davis Michael J,
Muthuchamy Mariappan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.777.15
Subject(s) - lymphatic system , microbiology and biotechnology , substance p , inflammation , signal transduction , mapk/erk pathway , receptor , chemistry , neurokinin a , crosstalk , contractility , biology , neuropeptide , immunology , endocrinology , biochemistry , physics , optics
The lymphatic system plays a key role in body fluid homeostasis, inflammation, lipid absorption and immunity, and these vital functions rely on the contractility of the lymphatic muscle cells (LMCs). Substance P (SP), a neuropeptide associated with the sensory innervation of lymphoid tissue, modulates lymphatic contraction by activating signaling cascades that control phosphorylation of myosin light chain (p‐MLC 20 ). SP is also a major regulator of inflammatory responses and inflammation alters lymphatic contractility. Hence, we hypothesize that SP activates both inflammatory and contractile signaling pathways through neurokinin receptors (NK1R, NK2R, NK3R) in lymphatics. To test this, we investigated the expression of NKRs and activation of pro‐inflammatory MAPK pathway by SP in LMCs. Results demonstrated expression of NK1R and NK3R in LMCs. SP treatment increased expression of p‐MLC 20 as well as p38 MAPK and pERK1/2, indicating activation of the MAPK pathway. Inhibition of both NK1R and NK3R affected SP signaling. Inhibition of ERK1/2 decreased levels of p‐MLC 20 after SP activation, while p38 inhibition did not. These data provide the first evidence that SP mediated crosstalk between pro‐inflammatory and contractile signaling mechanisms exists in the lymphatic system and may be an important bridge between lymphatic function modulation and inflammation. AHA 09POST2280005 to SC; NIH RO1 HL080526 to MM.