# Role of hemeoxygenase-1 in experimental acute pancreatitis

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $441,900

## Abstract

Acute pancreatitis (AP) remains a challenging clinical problem, particularly in patients with severe
disease. Despite its disease burden, therapy remains supportive at best coupled with removal of
precipitating factors that may include alcohol or biliary obstructing calculi. We showed a protective effect
and therapeutic role of hemin (hemoglobin prosthetic moiety that upregulates hemeoxygenase-1, HO-1)
in experimental AP via recruitment of HO-1+ F4/80+ cells to the pancreas. Moreover, we also elucidated
mechanism for beneficial effects of HO-1 downstream effectors. Given these results, we propose to test
the hypothesis that there is shift in immune response during recovery from AP as compare to acute
phases of AP and we propose here to understand these mechanisms in order to improve our
understanding of immune pathways that promote recovery and resolution of the inflammation. The
specific aims of our proposal are: Aim 1: Phenotypic and functional assessment. Here we will test the
hypothesis that resolution of AP is associated with an increased adaptive and decreased
monocyte/macrophage recruitment as compared to acute phase of AP. Aim 2: Cellular cross talk in the
pathogenesis of acute pancreatitis. Here we will test the hypothesis that activated pancreatic stellate
cells secrete factors that alter pro-inflammatory macrophages recruited during acute phase of AP into
suppressive macrophages that promote recovery. Aim 3: Innate immune activation and cell damage
associated signals in pancreatitis. Here we will test the hypothesis that unlike macrophages in acute
phase of AP, macrophages during recovery mediate recovery by suppressing T cell activation and
proliferation. During severe or acute phase of AP however, macrophages sense cellular damage
components and activate pathways that perpetuate pro-inflammatory cytokine release. Findings from this
project will allow for a better understanding of immune responses and infiltrates associated with acute
phases of AP and recovery. In addition to the gained understanding of immune mechanisms that
mediate and/or allow progression of AP and recovery, the potential impact of this project is of great
clinical significance, as our studies may lead to the development of novel therapies that can alter clinical
practice in a disease for which no active therapy is available.

## Key facts

- **NIH application ID:** 9903274
- **Project number:** 5R01DK092421-09
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Aida Habtezion
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $441,900
- **Award type:** 5
- **Project period:** 2011-09-20 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9903274

## Citation

> US National Institutes of Health, RePORTER application 9903274, Role of hemeoxygenase-1 in experimental acute pancreatitis (5R01DK092421-09). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9903274. Licensed CC0.

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