Fig. 5: CRH^PVN neurons regulate ALI through local sympathetic activation.

Plasma corticosterone (a) and lung NE (b) levels of PBS-treated, LPS-treated control, and LPS-treated hM3Dq mice (n = 6 mice per group). c Representative western blot and quantification of TH in lung tissue from control and hM3Dq mice (n = 3 mice per group). d Schematic of 6-OHDA treatment on CRH-IRES-Cre mice. e Representative images of lung TH in PBS- and 6-OHDA-treated mice. Scale bar: 50 μm. f Lung NE levels in LPS-treated control and LPS-treated hM3Dq mice with vehicle or 6-OHDA treatment (n = 6 mice per group). g Kaplan–Meier survival of LPS-treated control and LPS-treated hM3Dq mice with vehicle or 6-OHDA treatment (n = 12 mice per group). Flow cytometric quantification of CD45⁺ leukocytes (h) and Ly6G⁺ neutrophils (i), and total protein by BCA (j) in BALF from indicated groups (n = 7 mice per group). k Representative H&E images of the lung. Scale bar: 1 mm (low magnification), 50 μm (high magnification). l Lung injury score assessed from 15 sections/lung/mice (n = 5 mice per group). m Schematic diagram of ICI118551 (a specific β₂-AR antagonist) treatment on CRH-IRES-Cre mice subjected to ALI. Flow cytometric quantification of CD45⁺ leukocytes (n) and Ly6G⁺ neutrophils (o), and total protein (p) by BCA in BALF of LPS-treated control and LPS-treated hM3Dq mice with vehicle or ICI118551 (n = 6 mice per group). Representative lung H&E images (q) and lung injury scores (r) (n = 5 mice per group). Scale bar: 1 mm (low magnification), 50 μm (high magnification). Significance was determined by 1-way ANOVA with Tukey’s post-hoc multiple comparisons test (a, b, f, h–j, I, n–p, r), 2-tailed unpaired t-test (c), and Log-rank (Mantel–Cox) test (g). Data are presented as mean ± SEM. All experiments were repeated three times, yielding similar results. Source data are provided as a Source data file. ALI acute lung injury, BALF bronchoalveolar lavage fluid, CRH corticotropin-releasing hormone, H&E hematoxylin and eosin, LPS lipopolysaccharide, NE norepinephrine, PVN paraventricular nucleus, TH tyrosine hydroxylase, β₂-AR β₂ adrenergic receptor.