Fig. 4 |. iRHOM2 deficiency affects P. aeruginosa pneumonia and ADAM17 maturation and AREG secretion and function in lung epithelial cells.

a, Average of the change in body weight measurements for WT and Rhbdf2^−/− mice infected with P. aeruginosa pneumonia during infection (n = 15 per group). b, Percentage of WT and Rhbdf2^−/− mice who survived P. aeruginosa pneumonia averaged for total number of mice in each group over multiple trials of infection (n = 15 per group). Data are proportion ± s.e.m. c, Quantified c.f.u. of P. aeruginosa bacteria extracted from total lung tissue for each mouse (n = 4 per group). d, Lungs from Rhbdf2^−/− mice infected with 5 × 10⁸ c.f.u. of P. aeruginosa on day 3 following infection. Whole lung (left), lower magnification (middle) and higher magnification (right) are shown. Pulmonary hemorrhages are seen (yellow arrow). e, Bead-based multiplex assay measurements of TNF in mouse serum (n = 5 per group). f, Immunoblot of lung epithelial cells purified from two different WT or Rhbdf2^−/− (knockout (KO)) mice. Asterisk shows pro-ADAM17, and black arrowhead shows mature ADAM17. g, Immunoblot as in f, of A549, H1299 and PC9 lung tumor cells knocked out for the indicated targets. h, AREG measured by ELISA in cell culture supernatants of A549 cells treated with siRNAs as in Extended Data Fig. 4b (n = 7 per group). i, Wound healing assay in knockout A549 cells either with or without 50 ng ml⁻¹ each of AREG, TGF-α and HB-EGF as growth factors. Scratches were made and repair of the scratch was evaluated 24 h later. j, Quantification of wound healing measured in i (n = 9 per group). Representative results of two (f) or three (d,g) independent experiments. Two-tailed, unpaired Student’s t-test (a,e,h,j; mean ± s.d.) or Mann–Whitney test (c; mean ± s.e.m.) was used to calculate P value.