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rhCC10 Treatment Modulates the Pro and Anti‐Inflammatory Profile in the Immature Lung
Author(s) -
Hubert Terrence,
Wu Jichuan,
Park Yongsung,
Kato Kosuke,
Kimura Keita,
Shaffer Thomas,
Eguchi Satoru,
Kim Kwang Chul,
Wolfson Marla R.
Publication year - 2011
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.25.1_supplement.660.7
Subject(s) - lung , western blot , mucin , recombinant dna , inflammation , medicine , muc1 , endogeny , andrology , pulmonary surfactant , gastroenterology , chemistry , pathology , biochemistry , gene
Background Both CC10, a clara cell secreted protein, and Muc1, a membrane‐bound lung epithelia mucin, are present extracellularly, are anti‐inflammatory, and deficient in the immature lung. We have shown previously that surfactant treatment (SFT), followed by recombinant human CC10 (rhCC10) treatment, reduces inflammation (J Appl Physiol 2005;99:2204–11). However, it is unknown if there is a corresponding response to rhCC10 and SFT on the intrinsic pro/anti‐inflammatory milieu in the immature lung. Objective Assess the endogenous CC10 and Muc1 response to rhCC10 in the preterm lung. Methods 24 premature lambs (126 ± 3 SD days) were anesthetized, instrumented, delivered, paralyzed, and ventilated. Lambs were randomized to 4 groups (n=6/group) following baseline measurements: untreated (UNT), SFT (Survanta ® 100mg/kg; 4ml/kg), or SFT followed by intratracheal rhCC10 (0.5 or 1.5 mg/kg; 2 ml/kg). After 4 hrs, lung tissue was harvested for Muc1 and IL‐8 ELISAs, CC10 western blot, and qPCR analysis. ResultsTreatment Groups UNT SFT SFT + 0.5 mg/kg rhCC10 SFT + 1.5 mg/kg rhCC10Relative Endogenous CC10 mRNA Exp (x 10 −3 ) 6.93 ± 1.66 6.40 ± 3.60 8.29 ± 2.35 0.70 ± 0.41* Muc1 (Abs × 10 −3 ) 4.6 ± 0.20 3.9 ± 0.57 4.1 ± 0.87 3.0 ± 0.53* IL‐8 (ng/mg protein) 17.70 ± 2.11 21.58 ± 1.75 20.55 ± 1.71 12.85 ± 3.32*Mean ± SEM (*p < 0.05 vs other groups)Conclusions These data demonstrate that both pro‐ and anti‐inflammatory profiles in the immature lung are responsive to rhCC10 in a dose dependent manner. We speculate that the anti‐inflammatory action of rhCC10 down regulates intrinsic anti‐inflammatory pathways. Further work using lung epithelial cell culture to analyze downstream CC10 and Muc1 pathways and western analysis of CC10 are ongoing. Supp.: NIH 5T32HL091804; P20RR020173; RO1 HL‐47125; Clarassance, Inc. (Claragen, Inc.); Ross Labs.