# Inflammatory and Dysregulated Repair Responses to Inhaled Nicotine

> **NIH NIH R01** · UNIVERSITY OF ROCHESTER · 2021 · $432,989

## Abstract

SUMMARY
Nicotine is a major component of nicotine delivery systems [Electronic Nicotine Delivery Systems (ENDS)] i.e.
electronic cigarettes (e-cigs). Nicotine is known to have the addictive properties, and a knowledge gap exists
on how inhaled nicotine affects the pulmonary system. Our supporting data show that ENDS nicotine aerosol
delivery and exposure cause oxidative stress and inflammatory responses in human lung epithelial cells,
fibroblasts, and in mouse lungs. Currently, no information is available on the biological effects of e-cig
containing inhaled nicotine in humans and in mouse models. Inhaled nicotine may contribute to the
pathogenesis of lung diseases in particular via lung inflammation, injurious, and dysregulated repair
responses. We hypothesize that e-cig nicotine influences toxicity as evidenced by oxidative and inflammatory
responses in humans and in mouse models, leading to dysregulated repair and emphysematous responses.
Three specific aims are proposed to test this hypothesis:
Aim 1: Inhaled nicotine induces lung and systemic inflammatory mediators in human subjects
Determine the impact of inhaled nicotine in users and non-users of e-cigarettes. This will be accomplished by
monitoring biomarkers of exposure (inflammatory, exosomes and lipid mediators by lipidomics) in human
biofluids (saliva, Exhaled Breath Condensate, plasma, and urine) along with clinical outcomes (lung function
tests) in a prospective cohort study (baseline and follow-up). Along with human studies, we plan to conduct
mechanistic studies in vivo and in vitro.
Aim 2: Inhaled nicotine induces lung inflammatory and dysregulated repair responses via its receptor
Here, we will use a mouse preclinical model for mechanistic studies. We will determine if e-cigarettes
containing low and high nicotine concentrations have differential pro-inflammatory and abnormal repair effects
in vivo via the α7 nicotinic acetylcholine receptor (α7nAChR) dependent mechanism.
Aim 3: Mechanisms whereby nicotine aerosol induces inflammatory and dysregulated cellular repair
responses
Determine inflammatory and dysregulated cellular repair responses to e-cigarette nicotine vapor in human lung
epithelial cells and fibroblasts using the state-of-the-art reporter models (NF-κB luciferase) as well as a 3-D cell
culture model. This will determine how nicotine affects cellular processes, such as early cellular senescence
and myofibroblast differentiation, as well as lipogenic and myogenic pathways in healing/repair process.
 The outcomes of this study will provide an understanding of the clinical impact and mechanisms of
inflammatory, senescence, and dysregulated repair responses following nicotine exposure in human subjects
and, in primary lung cells in vitro and mouse model in vivo.

## Key facts

- **NIH application ID:** 10089469
- **Project number:** 5R01HL135613-05
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** IRFAN RAHMAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $432,989
- **Award type:** 5
- **Project period:** 2017-01-16 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089469

## Citation

> US National Institutes of Health, RePORTER application 10089469, Inflammatory and Dysregulated Repair Responses to Inhaled Nicotine (5R01HL135613-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10089469. Licensed CC0.

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