SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells.

Wang, Ying

Zhu, Zhou

Church, Tony D

Lugogo, Njira L

Que, Loretta G

Francisco, Dave

Ingram, Jennifer L

Huggins, Molly

Beaver, Denise M

Wright, Jo Rae

Kraft, Monica

2022-07-01T15:06:39Z

2022-07-01T15:06:39Z

2012-04

2022-07-01T15:06:38Z

Asthma is a chronic inflammatory disease in which airway epithelial cells are the first line of defense against exposure of the airway to infectious agents. Src homology protein (SHP)-1, a protein tyrosine phosphatase, is a negative regulator of signaling pathways that are critical to the development of asthma and host defense. We hypothesize that SHP-1 function is defective in asthma, contributing to the increased inflammatory response induced by Mycoplasma pneumoniae, a pathogen known to exacerbate asthma. M. pneumoniae significantly activated SHP-1 in airway epithelial cells collected from nonasthmatic subjects by bronchoscopy with airway brushing but not in cells from asthmatic subjects. In asthmatic airway epithelial cells, M. pneumoniae induced significant PI3K/Akt phosphorylation, NF-κB activation, and IL-8 production compared with nonasthmatic cells, which were reversed by SHP-1 overexpression. Conversely, SHP-1 knockdown significantly increased IL-8 production and PI3K/Akt and NF-κB activation in the setting of M. pneumoniae infection in nonasthmatic cells, but it did not exacerbate these three parameters already activated in asthmatic cells. Thus, SHP-1 plays a critical role in abrogating M. pneumoniae-induced IL-8 production in nonasthmatic airway epithelial cells through inhibition of PI3K/Akt and NF-κB activity, but it is defective in asthma, resulting in an enhanced inflammatory response to infection.

jimmunol.1100573

0022-1767

1550-6606

https://hdl.handle.net/10161/25438

eng

The American Association of Immunologists

Journal of immunology (Baltimore, Md. : 1950)

10.4049/jimmunol.1100573

Cells, Cultured

Cell Nucleus

Epithelial Cells

Bronchoalveolar Lavage Fluid

Humans

Mycoplasma pneumoniae

Asthma

Inflammation

NF-kappa B

RNA, Small Interfering

Interleukin-8

Transcription, Genetic

RNA Interference

Protein Processing, Post-Translational

Phosphorylation

Adult

Female

Male

Proto-Oncogene Proteins c-akt

Protein Tyrosine Phosphatase, Non-Receptor Type 6

Young Adult

Phosphatidylinositol 3-Kinases

In Vitro Techniques

SHP-1 as a critical regulator of Mycoplasma pneumoniae-induced inflammation in human asthmatic airway epithelial cells.

Journal article

Ingram, Jennifer L|0000-0002-5269-8864

3371

3381

7

Duke

School of Medicine

Faculty

Staff

Clinical Science Departments

Medicine

Pathology

Surgery

Medicine, Pulmonary, Allergy, and Critical Care Medicine

Surgery, Surgical Sciences

Published

188