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Histochemistry and Cell Biology

, Volume 147, Issue 3, pp 389–397 | Cite as

DMBT1 promotes basal and meconium-induced nitric oxide production in human lung epithelial cells in vitro

  • Hanna Müller
  • Christel Weiss
  • Marcus Renner
  • Ursula Felderhoff-Müser
  • Jan Mollenhauer
Original Paper

Abstract

Meconium aspiration syndrome (MAS) is characterized by surfactant inactivation and inflammation. As lung epithelial cells up-regulate nitric oxide (NO) in response to inflammation, the NO production following meconium exposition was examined in relation to expression of Deleted in Malignant Brain Tumors 1 (DMBT1), a protein with functions in innate immunity and inflammatory regulation. Here, DMBT1 expression was analyzed by immunohistochemistry in postmortem lung sections from patients with MAS. The lung epithelial cell line A549, stably transfected with a DMBT1 (DMBT1+ cells) expression plasmid or with an empty expression plasmid (DMBT1− cells), was exposed to meconium. NO was determined in dependence of aminoguanidine (inducible NO synthase inhibitor), steroids and lipopolysaccharide (LPS). DMBT1 is highly expressed in lungs with MAS. In the absence of meconium, DMBT1+ cells showed a higher NO production than the DMBT1− cells (p = 0.0090). Meconium led in DMBT1− and DMBT1+ cells to elevated NO levels (p < 0.0001), but with a higher NO level in DMBT1+ cells (p < 0.0001). Aminoguanidine, an iNOS inhibitor, reduced the higher NO production in DMBT1+ cells (p = 0.0476), but NO levels remained above NO production from DMBT1− cells (p = 0.0289). Dexamethasone diminished NO production in DMBT1+ cells after meconium exposition (p = 0.0076). Combined addition of LPS and meconium significantly increased NO production in both cell types (p < 0.0001). In comparison to exposure with only meconium, the combined addition of LPS and meconium to the cells increased NO levels in both DMBT1− cells (p = 0.0030) and DMBT1+ cells (p = 0.0028). In conclusion, basal and meconium-induced NO production in lung epithelial cells is positively regulated by DMBT1.

Keywords

DMBT1 Nitric oxide Meconium aspiration Inflammation 

Notes

Acknowledgments

This work was supported by the Lundbeckfonden Center of Excellence NanoCAN Grant, by the DAWN-2020 Project financed by Rektorspuljen SDU2020 program, and the MIO Project of the OUH Frontlinjepuljen.

Compliance with ethical standards

Conflict of interest

The authors declare that no conflict of interest exists.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Department of Pediatrics I, Neonatology, University Hospital EssenUniversity Duisburg-EssenEssenGermany
  2. 2.Division of Neonatology, Department of PediatricsUniversity of HeidelbergHeidelbergGermany
  3. 3.Institute of Medical Statistics and Biomathematics, Medical Faculty MannheimUniversity of HeidelbergMannheimGermany
  4. 4.Institute of PathologyUniversity of HeidelbergHeidelbergGermany
  5. 5.Lundbeckfonden Center of Excellence NanoCAN and Molecular Oncology, Institute for Molecular MedicineUniversity of Southern DenmarkOdense CDenmark

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