# REGULATION OF PRODUCTION OF GAMMA INTERFERON IN TUMOR DE

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 1988 · $116,506

## Abstract

We intend to investigate the basic mechanisms of cellular and humoral
regulation of mouse immune interferon (IFN-gamma) production.  The helper
and suppressor lymphocytes that regulate IFN-gamma production will be
characterized along with the IFN-gamma-producing lymphocytes.  Primary
T-lymphocyte lines will also be studied as possible producers and
regulators of IFN-gamma production. The growth factors interleukins-1
(IL-I) and 2 (IL-2) will be investigated as possible mediators of cellular
regulation of IFN-gamma production.  Phorbol esters, IL-2, and polypeptide
hormones such as vasopressin are cell activators and may help in IFN-gamma
production through a common second messenger (cyclic GMP?).  Further
improvement of IFN-gamma purification and characterization will be done by
lectin affinity chromatography, antibody affinity chromatography, gel
electrophoresis, and N-terminal amino acid analysis.  Monoclonal antibodies
will be produced to IFN-gamma to improve purification and for further
characterization of IFN-gamma in terms of biological activity and
relationship to other lymphokines.  Purified IFN-gamma should be ideal for
an objective assessment of its possible range of biological activities,
among which are: (1) immunoregulation; (2) antitumor and anticellular
activity; (3) regulation of differentiation; and (4) antiviral properties.
The mechanism of action of IFN-gamma at the molecular level will be studied
(if time permits) through assessment of its membrane effects, intermediary
metabolism effects, and cellular protein kinase activities.  The long-term
goal is to understand natural regulatory functions of IFN-gamma and to be
able to manipulate IFN-gamms activity in order to obtain desirable
immunological, antiviral, and antitumor activities of this lymphokine.
Considerable progress has been made with regards to regulation of
production of IFN-gamma.  (IL-2) can replace helper cell requirement for
IFN-gamma production.  Dibutyryl cyclic GMP, arachidonic acid and its
lipooxygenase products (such as leukotrienes), the neuropeptides:
arginine, vasopressin, and oxytocin, and the tumor promoter phorbol
myristic acetate can replace IL-2 requirement.  IL-2 help in IFN-gamma
production may involve release of second messenger signals arachidonic acid
and diacyglycerol from membrane phospholipids, activation of guanylate
cyclase, and activation of protein kinases such ss protein kinase C.  The
produced IFN-gamma was shown to cause B cell maturation. Antibodies of
predetermined specificity were produced to IFN-gsmme and should help in
purification and characterizstion.  (HF)

## Key facts

- **NIH application ID:** 3177743
- **Project number:** 5R01CA039048-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **SAM.gov UEI:** NNFQH1JAPEP3
- **Principal Investigator:** HOWARD M JOHNSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $116,506
- **Award type:** 5
- **Project period:** 1984-04-01 → 1988-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177743

## Citation

> US National Institutes of Health, RePORTER application 3177743, REGULATION OF PRODUCTION OF GAMMA INTERFERON IN TUMOR DE (5R01CA039048-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177743. Licensed CC0.

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