# FIBROBLAST ACTIVATION

> **NIH NIH R01** · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · 1991 · $181,975

## Abstract

Disorders of excessive (e.g., cirrhosis of liver, lung fibrosis) or
impaired fibrogenic response to tissue injury are problems encountered
frequently in contemporary clinical medicine, however, knowledge
concerning the cause and pathogenesis of these conditions is fragmentary.
Immune of nonimmune injury almost invariably precede fibrotic reactions.
The macrophage plays a central role in the normal healing of wounds and
likely plays a similar role in other fibrotic reactions. The macrophage
produces two classes of biological response modifiers, [interleukin 1
(IL-1) and transforming growth factor Beta (TGF) Beta] that are capable
of modulating a variety of fibroblast functions. Macrophages produce two
species of IL-1 termed Alpha and Beta that share only 22% amino acid
homology, yet both stimulate fibroblast proliferation and production of
collagen, hyaluronic acid, collagenase, tissue inhibitor of
metalloproteinase and prostaglandin (PGE2). Three species of TGFBeta,
termed TGFBeta1, TGFBeta2 and TGFBeta1,2 have been identified. TGFBeta1
has been most widely studied and is the predominant species in platelet.
TGFBeta1 is similar to IL-1Alpha and Beta in its effects on fibroblasts
(i.e., stimulates growth and synthesis of glycosaminoglycans and
collagen) except it does not stimulate collagenase production and is a
potent fibroblast chemoattractant and stimulates fibronectin synthesis.
TGFBeta is also produced by T cells and is found in platelets and most
other normal and neoplastic cells. This application is concerned with
defining the structure-function relationships of IL-1Alpha and Beta and
TGFBeta1 with respect to their effects on fibroblast biology. The
methodology to be used to accomplish these goals will involve 10
synthesizing peptides representing the deduced primary structure of IL-
1Alpha and Beta and TGFBeta1, 2) identifying peptides that exert similar
effects as the parent molecules on fibroblasts, 3) characterizing the
binding characteristics of the peptides and producing polyclonal and
monoclonal antibodies against peptides to react with parent molecules as
an alternative approach to study structure-function relationships, and 40
determining whether previously described T cell lymphokines having the
same effects as TGFBeta1 on fibroblasts are indeed TGFBeta1 or TGFBeta1-
related. These studies should contribute to our basic knowledge of the
structural requirements (primary amino acid sequence) of IL-1alpha and
Beta and TGFBeta1 necessary for these biological response modifiers to
modulate fibroblast function and could provide new avenues of approach to
the study and therapy o a variety of human disease characterized by
excessive or defective fibrotic responses.

## Key facts

- **NIH application ID:** 3155391
- **Project number:** 5R01AR026034-11
- **Recipient organization:** UNIVERSITY OF TENNESSEE HEALTH SCI CTR
- **SAM.gov UEI:** X1M1PN3KG3E7
- **Principal Investigator:** ARNOLD E POSTLETHWAITE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $181,975
- **Award type:** 5
- **Project period:** 1979-09-01 → 1993-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155391

## Citation

> US National Institutes of Health, RePORTER application 3155391, FIBROBLAST ACTIVATION (5R01AR026034-11). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3155391. Licensed CC0.

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