# Cigarette Smoke Extract Combined with LPS Upregulates PITPβ Expression in Chronic Pulmonary Inflammation and May Be Related to the EGFR/ERK Signaling Pathway

## TL;DR

Cigarette smoke and LPS increase PITPβ in lung inflammation, possibly through the EGFR/ERK pathway, suggesting PITPβ as a potential COPD treatment target.

## Contribution

Identifies PITPβ upregulation in COPD models linked to the EGFR/ERK pathway, proposing PITPβ as a novel therapeutic target.

## Key findings

- CSE and LPS exposure upregulates PITPβ, TNF-α, and IL-6 in COPD models.
- ERK inhibition reduces PITPβ and inflammatory markers, while ERK overexpression increases them.
- EGFR silencing decreases ERK phosphorylation and suppresses PITPβ and cytokine expression.

## Abstract

Dysregulated lipid metabolism is increasingly implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD), yet the role of lipid transporters in cigarette smoke (CS)-induced chronic pulmonary inflammation remains unclear. Phosphatidylinositol transfer protein β (PITPβ) is a key regulator of phospholipid transport and phosphatidylinositol (PI) homeostasis. This study aims to investigate the expression of PITPβ in a COPD model induced by cigarette smoke extract (CSE) and lipopolysaccharide (LPS) and to elucidate whether its upregulation is regulated by the epidermal growth factor receptor/extracellular signal-regulated kinase (EGFR/ERK) signaling pathway. This study established an in vivo model through combined CS and LPS exposure and an in vitro model through combined CSE and LPS treatment. In the rat model, significant pathological changes characteristic of COPD were observed, accompanied by marked upregulation of PITPβ, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) expression. In human alveolar epithelial A549 cells, combined CSE and LPS treatment not only upregulated PITPβ, TNF-α, and IL-6 expression but also enhanced the phosphorylation levels of EGFR and ERK. Inhibition or silencing of ERK reduces PITPβ expression and downregulates TNF-α and IL-6 levels, whereas overexpression of ERK produces the opposite effect. Silencing EGFR reduces ERK phosphorylation while simultaneously inhibiting PITPβ, TNF-α, and IL-6 expression. Furthermore, combining EGFR silencing with ERK inhibition further decreases PITPβ expression. These findings indicate that CSE combined with LPS induces PITPβ upregulation in chronic pulmonary inflammation, with the EGFR/ERK signaling pathway at least partially mediating this process. This suggests that PITPβ may serve as a potential therapeutic target for COPD.